levels high because of fear of hypoglycemia, 3) those who want to become pregnant (I hope that
is not part of our clinic) and 4) those with hypoglycemia unawareness. The talks were
interesting but I am afraid I did not come away with many take home messages that you are
dying to hear. There was also a section on telemedicine Sunday morning but most of it does not
pertain to our patients right now. Dr. Ruth Weinstock from Syracuse talked about telehealth.
She mentioned that more than 50% of the hospitals now use telecommunication to some degree
and that there will be eight hundred thousand consultations in the United States this year via
telemedicine. There can be video conferencing where physicians can deal one on one with
patients. In some cases the results are as good as face-to-face contact and others there is little
improvement whatsoever. Thirty-four percent of the consultants felt they could have done better
with a face-to-face session than over the line. Teleconferences are particularly useful to rural
care providers where the experts can provide lectures and case review. She was talking more
about contact to physicians than to patients. Amy Tenderich, MA again talked about social
media. She mentioned many of the sites that I have already discussed. She also mentioned
diabeticconnect.com which I had not noted at the earlier talk. I realize I am giving a very
superficial overview of what is a very important phenomenon in the world now. We are naïve to
think that our patients do not learn a good deal about their diabetes from Facebook, Twitter and
online. We just have to be careful to make sure they understand that anything they hear or learn
should be digested properly and evaluated for its validity. Far too often the approach is “well it
is on the internet so it must be right”. We must move from that mentality if we want to avoid
serious problems. I was also interested in the emphasis by several speakers for anonymity for
participants. Apparently there are people who take advantage of real names and real patients in
ways that I do not quite understand. Please be on your guard when using any social media to
make certain that you are not compromising yourself or your child.
Pediatrics
I wanted to lump together several studies that have in common only that they deal with
children. You will see it is a bit of a potpourri of ideas. First there was a study from Seattle
looking at rural versus urban quality of care. They interviewed 34 rural and 27 urban care givers
of children with diabetes between the age of 2 and 18. The groups were pretty similar in terms
of age and length of diabetes. The only real difference was that 56% of the rural patients versus
15% of the urban were on Medicaid. They found that 4% of the urban children versus 30% of
the rural had been hospitalized one or more times for DKA. The urban group averaged more
clinic visits than the rural group (4.1 versus 3.6 per year). There was a bit of a difference in
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hemoglobin A1c (9.0% for rural and 8.5% for urban) but that was not statistically significant and
the 47% of the rural and 52% of the urban patients were on pump therapy. They asked the rural
participants why they travelled so far for care and 33% reported “no other option” and 44%
reported “it is worth it to receive the best possible care”. Sixty-seven percent of the respondents,
however, noted that travel was a hardship particularly in terms of financial impact of travel and
time off of work. Their conclusion was a little weak saying “strategies to address local support
for families living in rural areas may be beneficial”. I have looked at my patients over the years
and compared the hemoglobin A1c levels for the patients who are seen at the mother ship versus
patients who are seen in Outreach. There really is no difference in terms of hemoglobin A1c. I
cannot address the question of DKA, however. It would be interesting to try to track that down.
I can very much sympathize with all of our patients who come two or three hours to come to
Outreach clinic. Hopefully we can find a good alternative (intermittent telemedicine comes to
mind) that may make their life easier. Along those lines was a study from Boston looking at
telehealth for management of Type I diabetes in high risk adolescents. They looked at 12
subjects who were divided evenly to receive standard care as they do in their clinic. The other
16 patients had a monthly video conference “visit” with a diabetes nurse educator and a social
worker for six months, focusing on diabetes self-management and social supports. There were a
total of 12 “visits” along with the usual diabetes care. Baseline hemoglobin A1c levels were
pretty similar with 9.36% for the control group and 9.0% for the telehealth group. Eighty-eight
percent of the patients completed at least one diabetes nurse educator visit and 75% completed at
least five diabetes nurse visits. Eighty-one percent completed at least one social work visit and
69% completed at least five social work visits. There was no difference at six months in the
change in Hemoglobin A1c between the two groups (control patients dropped 0.82% and
telehealth patients dropped 0.35% which was not statistically significant). They concluded, 1)
that a telehealth intervention with up to 12 visits over six months is a feasible method of
increasing interaction between adolescents and their diabetes team and 2) “although there was no
effect on hemoglobin A1c, additional analyses will examine the intermediate impact of increased
interaction on diabetes self management and inform the design of larger, more definitive trial”.
It is important to remember that these patients also received standard care which meant that
they were seen routinely in clinic as they had been before. The telehealth was in addition to
standard care and did make a difference although it was not statistically significant. A group
from Portland, Oregon profiled youth who were repeatedly hospitalized for DKA. The question
was, “Are they all in poor control?” They looked retrospectively at a group of Type I diabetics
who were chronically poorly controlled and compared them with a sample of youth with Type I
diabetes who were repeatedly hospitalized for DKA. They defined repeatedly as three bouts of
DKA in five months. They found that the youth with poorly controlled diabetes were
significantly younger. There were no other significant differences between the groups in terms
of parental status, gender, ethnicity, duration of diabetes and general parent/child conflict. They
concluded “while preliminary, these findings suggest that older youth may be at higher risk for
DKA. Additionally, glycemic control may not be a proxy for risk of repeated DKA episodes in
youth with Type I diabetes”. We have never tried to do a comparison study like this. It is not
surprising that older children run into trouble because first, they are at a greater level of puberty
and the hormones of puberty have a profound effect in the development of ketoacidosis and
second, they are undoubtedly given more independence by the family and thus are more likely to
sink or swim on their own. I am not sure if there is much more to be taken from this study.
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A group from Nashville, Tennessee along with the Joslin Diabetes Center in Boston
looked at factors that were related to teen’s technology use. They reported that most teens (79%)
and parents (76%) used at least one form of technology for diabetes care. Patients who used
insulin pumps were 5.7 times more likely to use online social sites for diabetes than non-pump
users. Girls were 2.4 times more likely than boys to use diabetes websites. They concluded
“findings have practical implications to support technology mediated interventions to improve
diabetes self management in teens. Targeting both teens and their parents may be beneficial”.
There is that ugly ‘T’ word again. Obviously we need to be training our patients better at
finding appropriate sites that might be useful for them. I smell a new project coming up. The
Joslin Clinic group combined with the Barbara Davis Center to look at glucose levels assessed
by continuous glucose monitoring across the pediatric age range. Their intent was to assess
glucose extremes and mean glucose levels by time of day in children between 2 and 17 years of
age. They were using the Dexcom G4 platinum CGM system. They found that the CGM
performance was similar across the age groups. They worked equally well for all ages. They
also found that during the seven day CGM session, mean blood glucose level and the proportion
greater than 240 mg/dL were highest in the 2 to 5 year olds and that the proportion less than 70
mg/dL was lowest in the same group. They found that all age groups experienced substantial
hyperglycemia with somewhere between 1/5 and 1/3 of all CGM values greater than 240 mg/dL.
Their results are in the following chart.
I think the results are fairly self-explanatory. I am a little bit surprised that the 13 to 17 year
olds did not have a greater portion of blood sugars greater than 240 mg/dL. This is the age
group where we encounter the highest hemoglobin A1c levels. It just goes to show that we have
a long way to go to smooth out diabetes management. The Joslin group also looked at
biomedical predictors of consistent use of continuous glucose monitoring in youth. They looked
at 61 youth between 8 and 17 years of age who were on CGM. They found that at three months
after the start of CGM, the mean CGM use was 99.6 hours per week and at six months the mean
CGM use was 82.5 hours per week. Eight of the subjects had stopped using CGM by three
months and 12 by six months. Approximately one third of the children (36%) were using CGM
consistently as defined as six to seven days per week at six months of use. They found that
consistent CGM use at six months was associated with more frequent blood glucose monitoring
and a lower hemoglobin A1c (7.5% versus 7.9%) compared to patients who used CGM zero to
five days per week. The children using CGM six to seven times per week had a 4.2 times greater
chance of meeting the ADA target of a hemoglobin A1c of less than 7.5% (59% among the six to
seven days per use group versus 26% in the zero to six days per week group). Not surprisingly,
they found that reported missed insulin dosing was less likely to occur in youth using CGM six
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to seven days per week than in those who were not (18% versus 47%). They concluded “in
pediatric patients, consistent CGM use appears to be associated with greater blood glucose
monitoring frequency rather than decreased blood glucose monitoring frequency, suggesting that
attention to CGM data leads to greater treatment adherence with more blood glucose checks and
insulin administration”. I was surprised that they found that the consistent CGM patients did
more blood glucose monitoring than the others. Intuitively I would have felt it would be the
other way around. It is encouraging to see an improvement in hemoglobin A1c with CGM use.
A group from Columbus, Ohio looked at the effect of vitamin D supplementation on the
frequency of partial clinical remission period in children and adolescents with newly diagnosed
Type I diabetes. They were working on the fact that “growing evidence suggests vitamin D may
play a role in the natural progression of Type I diabetes by altering endogenous insulin secretion
and influencing systemic inflammation”. They were looking at how long the partial clinical
remission or honeymoon period lasted in patients given vitamin D versus a group that was not.
They found that there was no statistical difference between the two groups at nine months after
diagnosis. They concluded “our study indicates vitamin D supplementation does not
significantly improve frequency of PCR period in children and adolescents with newly diagnosed
Type I diabetes”. This does not mean that patients needing vitamin D should not receive it. It
just does not prolong the honeymoon phase. A group from Japan did a randomized crossover
study of the efficacy and safety of switching from insulin glargine to insulin Degludec in
children with Type I diabetes. They studied 18 patients who had an average age of 11.7 years.
They used a randomized crossover design where they compared fasting plasma glucose levels,
hemoglobin A1c levels and frequency of hypoglycemia (glucose less than 70 mg/dL) at the
twelfth week. The fasting blood glucose levels at 12 weeks were 134.9 mg/dL for glargine and
133.8 mg/dL for Degludec. The hemoglobin A1c in both cases were 7.8%. The frequency of
overall hypoglycemia was similar (4.2% versus 3.4% episodes per month). Nocturnal
hypoglycemia was significantly lower in insulin Degludec, however, with a rate of 0.8 episodes
per month versus 1.8 episodes per month with glargine. The daily insulin dose was not
significantly different. The patients required 0.48 U/kg/day on glargine and 0.44 U/kg/day of
Degludec. They concluded “these results suggest that insulin Degludec given once at bedtime
provides similar glycemic control to insulin glargine while lowering a risk of nocturnal
hypoglycemia”. There were three studies again looking at the transition from pediatric care to
adult care. I am choosing not to include their results because they are very similar to the studies
I have quoted in past years. This continues to be an ongoing worry and concern. The group
from Joslin in Boston looked at the impact of hemoglobin A1c and BMI on blood pressure over
time in pediatrics. I will not go through all of their data but their conclusion was “increases in
A1c lead to small increases in systolic blood pressure and diastolic blood pressure: ZBMI and
baseline blood pressure strongly influence blood pressure changes”. Finally, a group from
Hanover, Germany looked at diabetes, autoimmunity and psyche: comorbidities are frequent in
children. They looked at a group of 594 children and adolescents with Type I diabetes. They
had an average age of 13 years and had had Type I diabetes for 5.3 years. Their average
hemoglobin A1c was 7.9%. Thirty-one percent of the patients suffered from at least one further
autoimmune disease (autoimmune thyroiditis 26%, celiac disease 7%, vitiligo 1%, autoimmune
hepatitis and rheumatoid arthritis less than 1%). A psychiatric or behavioral disorder was
diagnosed in 26.4% of the patients. Patients with autoimmune disease were more frequently
female, older and had a longer duration of Type I diabetes. They also had higher insulin
requirements and a greater prevalence of lipodystrophy at injection sites. Patients with
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psychiatric disorders were older and had worse glycemic control than those without. They also
had a greater frequency of severe hypoglycemia although their frequency of monthly
hypoglycemia was actually less. They concluded “among young patients with Type I diabetes,
every third is affected from another chronic autoimmune disease while every fourth may have
additionally a psychiatric/behavioral disorder”. I was not surprised at the frequency of
autoimmune thyroiditis. An important factor, however, is that usually less than half of these
patients ever require treatment. Their rate of 7% celiac disease is very similar to what we find
in the States. Obviously all of these patients are treated. I do not know what to say about the
psychiatric disorders. We are acutely aware that many of our patients have problems
particularly with depression and anxiety. I cannot quote numbers as to the frequency in our
clinic. This study is important because it does point out why we do routine screening for thyroid
and celiac disease on a fairly frequent basis. It also indicates why we have two social workers in
our clinic. So that is all that I found of interest in the pediatric section. I hope that some of this
information was either new or helpful to you.
Miscellaneous
If you thought that the studies put together in the last section were somewhat random,
wait till you see what I have here. These are studies that I thought were interesting and might be
interesting to you but I could find no other place to put them. The first study was from Boston
but not from the pediatric group. It was about the association of continuous subcutaneous insulin
injection pumps with lower hemoglobin A1c and mortality in Type I diabetes of chronic
duration. This was part of their 50 Year Medalist study in which they investigated 944
individuals with more than 50 years of Type I diabetes. The average age was 65 years and the
average hemoglobin A1c was 7.1%. Fifty-nine percent used CSII, 49% for longer than 10 years.
During the last 12 years 94 participants (10%) passed away, 32 using CSII (6% of the total
group) and 62 using MDI (16%). Forty-four percent died from cardiovascular disease, 10% from
cancer, 7% from direct complications of diabetes and 7% due to accidents. They found that CSII
use was associated with reduced mortality (hazard ratio 0.42). They found that hazard increases
by 1.09 for each unit (%) change in hemoglobin A1c for MDI compared to 1.3 for CSII. They
concluded “CSII may reduce hemoglobin A1c and mitigate other risk factors, reducing mortality
among individuals with chronic duration of Type I diabetes. Some of my partners feel that I have
been following patients this long but I protest that I have no one who is a 50 Year Medalist. As
you remember from the last two years, there was a great deal of interest and talk about
hyaluronidase use. It is an enzymatic tissue modifier that degrades the glucose aminoglycan
layer in subcutaneous space, resulting in an ultrafast insulin action profile. I could find only two
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papers dealing with hyaluronidase this year which is a marked decrease from the last two years.
The first study was from the Barbara Davis Center in Denver. They were looking to see if
hyaluronidase use in an outpatient setting would lower total daily dose of insulin or effect mean
glucose values. They have had three subjects so far complete their study. They saw no
differences when compared to control patients in total daily dose of insulin, average daily
glucose or percent of sensor glucose in target. They concluded “in this initial cohort,
hyaluronidase use at pump infusion sites did not affect insulin total daily dose or alter glycemic
control”.
The other study again came from Colorado along with Stanford. They were looking at the
injection site survival in patients who received hyaluronidase. It turns out these are the same 13
patients mentioned in the earlier study. They found that the median duration of set survival was
5.2 days with hyaluronidase use versus 5.7 days in non-hyaluronidase. They concluded that the
use of hyaluronidase injected into the insulin pump infusion site does not appear to prolong the
duration of infusion set wear.
The ardor for hyaluronidase use has diminished tremendously. I am not quite sure what the
problem was but obviously people are running into enough issues that they are jumping off the
bandwagon. I was hoping that it might be useful to speed up insulin but I suspect we are just
going to have to use the newer insulins that I mentioned in the earlier section. This segways
very nicely into the papers on the InsuPad. As you may remember from last year, the InsuPad
chemically warms up the infusion site for insulin pump users and in theory speeds up the
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absorption of the insulin. The first study came from Mainz, Germany. They stated
“improvement of blood flow at the insulin injection site as induced by the InsuPad device leads
to a more efficient and consistent uptake of prandial insulin, resulting in better glycemic control,
less hypoglycemic events and lower prandial insulin dose requirements in previous controlled
clinical studies”. This was a post marketing study which means that the device is now available
in Germany. Three hundred and forty patients with diabetes were included in the analysis.
During the 11 weeks of the study there was a significant reduction in hemoglobin A1c (-0.65%)
and in body weight (1.0 kg). The frequency of hypoglycemia and hyperglycemia both decreased
(-44% and -35%). Participants also noted a lower prandial and basal insulin dose requirement (12% and -8% respectively). There were 14 reports about skin reactions using the device
(14.1%). Interestingly 12.1% of the participants reported less occurrence of lipodystrophy.
They concluded “the results from this post marketing surveillance study confirm that these trial
results also translate into similar benefits when the device is used in daily routine treatment
practice”. Another study from the same group looked at the use of regular insulin rather than the
analogs that you all use. They found “use of InsuPad device in daily treatment routine in people
with diabetes on intensive insulin treatment using regular insulin as prandial insulin component
resulted in improvement in glycemic control (better hemoglobin A1c, less hypoglycemia, lower
insulin dose requirements) as was demonstrated with diabetic patients using short acting insulin
analogs”. A group from Jerusalem looked at the effect of injection site treatment with the
InsuPad on regular and analog insulin pharmacokinetics. I just wanted to show their graph to
show that the glucose levels were significantly lower with the use of the InsuPad. This study
was interesting because they again compared patients on regular insulin, which is considerably
slower than the analogs, who use the InsuPad versus patients on analog insulin (Humalog,
NovoLog, and Apidra) but without the InsuPad. As you can see, the heat resulted in a lower
glucose profile even with regular insulin.
This is a telling paper and shows that the InsuPad really does make a difference. We would not
want to revert back to regular insulin but if we see that change with regular insulin you can
imagine the change with the analogs. A group from New Haven looked at a different device
called the InsuPatch which also warms up the infusion site. They looked at nine patients using a
Medtronic pump. They compared the use of the InsuPatch versus the same patients without the
InsuPatch. The InsuPatch, by the way, warms the site to 40º Celsius. Their results are in the
following table.
34
They concluded “skin warming with InsuPatch did not result in faster insulin kinetics in a closed
loop setting. Larger manual prandial insulin doses may be necessary for optimal effect of
infusion site warming”. Thus we have some studies showing that these heating devices are
useful and one study showing that it did not make much difference. There will be more studies
before these devices will be allowed in the United States. One drawback that I saw was that
these devices are fairly large. They are not just a small little patch like the infusion sets. Some
of our patients might find them fairly cumbersome.
For all you wine drinkers I wanted to include a study from Amsterdam, Netherlands.
They were looking at red wine polyphenols as treatment for obesity associated insulin resistance.
They did a placebo controlled, double blind clinical trial to see if the use of red wine helped with
insulin resistance. The idea is based on the fact that “red wine consumption is associated with
reduced incidence of Type II diabetes. Preclinical studies suggest that polyphenols extracted
from red wine favorably affect insulin sensitivity. Unfortunately they did not find that to be the
case in these patients who were already insulin resistant. I will not show the chart but their
conclusion was “eight weeks of RWPS supplementation do not improve insulin sensitivity, post
prandial glycemia or lipid levels in obese mildly insulin resistant volunteer”. Nuts. I guess I
cannot prescribe red wine to my patients anymore. Finally there was a paper from a variety of
places including Yale, Buffalo and the Barbara Davis Center looking at the use of glucagon nasal
powder. They pointed out that intramuscular glucagon is the only currently available treatment
for severe hypoglycemia outside of the hospital setting. They also pointed out “unlike current
IM emergency kits, needle-free dry powder intranasal glucagon does not require reconstitution
prior to administration”. They were looking at the efficacy of its use in 45 youth with Type I
diabetes. They had three cohorts ranging from 4 to less than 8 years of age, 8 to less than 12
years of age and 12 to less than 17 years of age. The two youngest cohorts were randomized in a
double blind format to one IM or two intranasal administrations. The older group received
randomly assigned 1 mg of IM glucagon and 3 mg of intranasal glucagon at another session.
Their results were “an increase in glucose greater than 25 mg/dL within 20 minutes of treatment
was observed in all but one intranasal participant (who immediately blew his nose following his
2 mg dosage). Nausea (with or without vomiting) occurred in 60% of patients receiving IM
glucagon and 42% in those receiving intranasal glucagon. They felt that “these data support the
efficacy and safety of a novel glucagon nasal powder delivery system for treatment of
hypoglycemia in youth with Type I diabetes”.
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An interesting idea that hopefully might be considerably cheaper. The cost of IM glucagon is
huge since we rarely need to use it. It also is extremely frightening to schools and other
associates to use an IM injection. Intranasal might well be much more accepted. This is the first
time I have heard of this approach and I suspect we will see more about it before it ever becomes
available. I hope that it will become available because it would be a nice addition for all of you.
Behavioral Aspects of Diabetes
I did not want you to think that I ignored the psychologists entirely at the meetings this
year. I did not go to most of their sessions because they did not have topics that I felt germane to
our clinic. Nevertheless they had many ongoing symposia. I wanted to present some posters and
oral presentations, however. First was a poster from Joslin Clinic in Boston which was
addressing readiness for independent self care. They developed a new questionnaire RIS-Q (the
readiness for independent self care questionnaire) and were testing to see if it seemed valid. It
included eight items on knowledge and 15 items on behaviors needed for self care and transition
to more independence plus five items for what the patient perceived as important. They found
that the teen and parent scores were highly correlated. Higher teen and parent scores were
associated with older age, less parental involvement in care, higher diabetes specific self-efficacy
and higher treatment adherence. The higher RIS-Q score was associated with less depressive
symptoms and less parent report of diabetes burden. They found girls had higher RIS-Q scores
than boys (boys know that this does not mean the girls are better, it’s just that they are better at
taking questionnaires). Interestingly, the RIS-Q score was not associated with hemoglobin A1c
level or insulin regimen. The results are shown on the following table.
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This is a questionnaire generated only for Joslin at this time. I suspect that our social workers
would be able to obtain a copy from them, however. It would be nice to have an objective way of
seeing if our teenagers were prepared for more independence. This brings up another topic,
however. The questionnaire was designed to see if teenagers were ready for more independence,
not fourth graders. We have an ongoing issue in our clinic of parents trying to give more
independence to fourth, fifth, sixth and seventh graders that results in disaster. Patients of this
age simply are not ready for independence despite how much their parents want them to be more
in charge. Joslin was looking at an older group and even they found that there were quite a bit
of variances within the patients. Please do not fall into that trap that late elementary and early
junior high students are ready for independence. Barbara Anderson from Houston along with
the Joslin group looked at the CES-D questionnaire to determine depressive symptoms among
teenagers. Unfortunately they did not tell us what the initials stand for. They surveyed 287
teens and they found that a positive CES-D screen was associated with girls, non-pump
treatment, youth reporting diabetes family conflict and diabetes burden, lower adherence and
lower quality of life. The parents also reported higher diabetes burden and lower quality of life.
This questionnaire is designed to determine patients at risk for depression and not for patients
already diagnosed with depression. They concluded “understanding teens with no depressive
symptoms may yield research directions on protective factors for glycemic control and quality of
life in teens with Type I diabetes”. I would think that the questionnaire also would help us
determine who is at risk and perhaps intervene a little bit earlier. Again, this is a questionnaire
that our social workers could look into. A group from Chapel Hill, North Carolina looked at
socioeconomic, demographic and clinical correlates of poor glycemic control. They used a
questionnaire on 758 patients aged 10 to 17 years old via the SEARCH for diabetes in youth
study. Poor glycemic control was defined as a hemoglobin A1c level of greater than or equal to
9.5%. Four hundred and ninety-five of the children and adolescents were on pump therapy, 118
basal bolus injections and 145 mixed insulin regimens. Twenty-six percent of the pump patients,
42% of the basal bolus injection patients and 55% of the mixed insulin regimen patients had poor
glycemic control. This is not at all surprising since the mixed insulin regimen which includes
insulins that most of you have never heard of is usually left for the patients where no other
approach has had any success whatsoever. They found among pump patients, poor control was
significantly associated with non-white race, being on Medicaid and decreased insulin
adherence. Patients on basal bolus injections showed that a correlation with decreased insulin
adherence. For the patients on mixed insulin regimen, the correlation for poor control was with
living in multiple households and having Medicaid insurance. Family conflict was really the
only factor that was significantly associated with poor glycemic control in all of the groups.
They concluded “a high percentage of U.S. youth with Type I diabetes had poor glycemic
control, especially those not on insulin pump. The strong association between family conflict
and poor glycemic control regardless of insulin regimen suggests a need to develop effective
management strategies that address this factor”. I guess I could have told them before they did
their study that family stress and poor adherence were pretty good indicators of poor control. It
is nice to have this documented but it still does not address the question of how we can overcome
these issues. However, the first step is to define the problem then we can move on to try to
address the solutions. A group of from Oklahoma City looked at the impact of Type I diabetes
knowledge, depression and anxiety on the hemoglobin A1c in young adults. They were looking
at patients between 15 and 23 years of age so I think that it still germane to our group. The
patients and parents completed a knowledge tool, a center developed instrument based on
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diabetes self-management education curriculum topics. The young adults also completed the
Minnesota Multiphasic Personality Inventory which assesses psychological functioning. The
average age of the “young adults” was 16.5 years and they had had diabetes for an average of six
years. They found that the higher the parents knowledge score, the lower the hemoglobin A1c
level in young adults while the higher depression and anxiety scores were associated with higher
A1c levels in young adults. They concluded “these results suggest that parent’s diabetes
knowledge and the emotional health of patients are important factors associated with hemoglobin
A1c in young adults with Type I diabetes. As the impact of parental diabetes knowledge on
young adult A1c is large, it is plausible that a lack of parental oversight leads to a fall in
glycemic control”. This study merely mirrors the one I mentioned before. Our teenagers are not
ready to assume all care for their diabetes. Parental involvement remains critical. (I made that
plural because earlier studies have shown that father’s involvement has a disproportionately
large impact on teens diabetes management) and that this impact cannot be lessened abruptly.
The transition to independence is a slow process over years and must be accepted as that even
though the teen wants to be more independent. We try not to allow that type of independence for
school, driving or lifestyle. I do not know why we should expect it in diabetes.
Another study from Pittsburgh looked at young adults with Type I diabetes (age 18 to 36
years) and the degree of partner involvement. These were patients who had a “romantic
relationship”. This of course included spouses but also serious significant others. They found
that the majority of participants found their partners level of involvement to be “just right” (68%)
but 6% found the partners were “too involved” and 26% found their partners were “not involved
enough”. The patients who said their partners were not involved enough received less support,
reported greater partner avoidance and higher levels of stress. They found that partner
controlling behavior was more bothersome for males and partner avoidance was more
bothersome for females. Interestingly the group that claimed that their partners were too
involved received greater support and had a stronger relationship. We need to consider this issue
as our patients move on. So often we assume that our patients are educating their significant
others but we probably need to have a more formal approach. I am not talking about the 16year-old crush but the patients who are moving on to presumably long-term relationships. Our
young adults in Utah tend to get married earlier than in other states so this is probably a topic
that we should address before they even leave the pediatric clinic. Not that I am encouraging
early romantic relationships, of course. A group from Charlottesville, Virginia looked at the
anatomy of driving mishaps by Type I drivers. They noted that the literature attributes much of
the driving problems to a subgroup of patients with peripheral neuropathy and problematic
hypoglycemia. However, one pediatric and one adult study has demonstrated that extreme
hyperglycemia disrupts cognitive motor functioning central to safe driving and one other study in
adolescents attributed citations and collisions to both hypo- and hyperglycemia. They took a
group of 122 Type I diabetic drivers categorized as low risk, 123 diabetic drivers categorized as
high risk of driving mishaps and 245 high risk drivers who received an intervention from them to
reduce future driving mishaps. The patients were questioned monthly for a year about
experiences with collisions, being stopped by police, losing control of the vehicle, having
someone take control of the vehicle, automatic driving and non-violational stopping. The results
are in the following table.
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They concluded “these data affirm that both hypo- and hyperglycemia impact driving in a variety
of ways. Having others take control occurred 368% more often among high risk which may
explain high risk drivers not having more collisions/citations. Intervention leads to prevention”.
Obviously this is a topic that we discuss frequently with our older teens. Once again the studies
indicate that hyperglycemia can be just as worrisome on the road as hypoglycemia. Hence the
requirement that patients test their blood before driving. I am afraid that many of us do not
enforce this requirement as much as we should and we really should put more emphasis on it.
Finally, a summary each year would not be complete without some reference to the Ready-Girls
program that Pittsburgh has been running for 15 years. You remember that I have referred to
them multiple times over the years and have mentioned their handouts for safe and responsible
sexuality in teenage girls with diabetes. They did a follow-up study on many of the girls who
have now reached adulthood. They found that these women engaged in preconception self care
with their healthcare providers to a varying degree. Forty-four percent discussed pregnancy,
29% discussed diabetes and sexuality, 75% discussed birth control and 37% had preconception
counseling. They concluded “these findings support the importance of the healthcare provider
initiating preconception counseling with adolescents to promote discussions in seeking
preconception counseling as adults”. Obviously I feel that this is a very serious topic due to the
incredibly higher risk of birth defects to babies conceived unintentionally when their mothers
have poor control and because of the profound negative effect it can have on a woman’s body
when she is out of control at the time of conception. I will say, however, that the rate of
unplanned pregnancy has diminished in my group of patients considerably. I do not have
numbers, unfortunately, but this problem is occurring considerably less often than it did in the
1990s. This is not due to lack of sexual activity since more girls are using birth control but to
sufficient awareness to know that precautions need to be taken before any action is undertaken.
In looking over my notes I see that I did attend one behavioral symposium. It was the
last session of the last full day of the conference and it just goes to show that fatigue does set in
and after a while you forget what you have done. The session was called “A ‘How to’ Guide for
the High Risk Patient”. This was dealing primarily with adults but there were a few small tidbits
that I thought would be interesting but I will not go through the full session. Felicia Hill-Briggs,
PhD from Johns Hopkins in Baltimore talked about the problem solving solution. She brought
up a couple interesting points. First off, the average literacy of diabetic patients across the
country is slightly less than fifth grade. Again, we are talking adults here. I would hope that our
patients are considerably more literate than that but we do have to recognize limitations. She
talked about the problem solving solution as a series of cognitive operations used to figure out
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what to do when the way to a goal is not apparent. This can include simple things like helping
with determining which insulin to change for a given problem or how to approach the behavioral
aspects of simply not eating properly or not adhering to their care plan. Her program includes 8
to 16 sessions that last anywhere from one and a half to two hours each. It helps enable self
management skills. The emphasis is on the accessibility of health information and the usability
of health information. I wish we had the manpower and the financial resources to try a system
like this with our teenagers to improve problem solving. Certainly many would be completely
disinterested and it would not help at all. I have to think, however, it would be beneficial for
some of our patients who simply are not succeeding. Janice Zgibor, PhD talked about what to try
when everything else fails. She mentioned a problem that I bring up with my patients all the
time which is clinical inertia. This is defined as the lack of movement or activity when change is
needed. She utilizes case management by CDEs and frequent contact with the patient. She did
make one very important point, however. “People with diabetes are more than their A1c level.”
The latter point is very important. That is why I try not to look at the A1c until the conclusion of
our session. I do not want you to ever think that I think of you only as a number. An A1c is
critically important but it is not the end all. Case management has been tried with our CDEs in
the past and they are just too stretched to do too much of that right now. I do think it would be
an excellent approach to some of our problem patients. The question of clinical inertia is
brought up in clinic a lot. I equate it to Albert Einstein’s definition of insanity: doing the same
thing expecting different results. We have to keep trying to convince our patients that if
something is not working, a different approach is necessary. Oh well, small steps at a time.
Henry Rodriguez, M.D. from Florida talked about strategies to suggest for the teen/young adult
and parent dyad. He pointed out that from 2001 to 2009, the prevalence of Type I diabetes
increased 21% while the prevalence of Type II diabetes increased 30%. He felt that the
management challenges for our teens and young adults are 1) the loss of supervision by the
pediatric team, 2) feeling invincible (also in terms of alcohol, drugs and sex), 3) changing
residence and 4) one third of adolescents with Type I diabetes have some type of psychiatric
disorder which includes eating disorders. He pointed out that literacy and numeracy can be the
key factors. He stated that we should develop strategies together to have an explicitly agreed
upon goals. He also emphasized that it needs to be an incremental approach rather than changing
everything at once. He suggested that patients download weekly or use written records such as
the “refrigerator records” that I use with my patients frequently. He also felt that we needed
better tools to help the transition. The adult endocrinologists are receiving these patients at just
the wrong stage of development and at the wrong time. And there you have it. I did not attend
the psychological sessions as much as perhaps I should. I will try to remedy that problem next
year.
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Non-Insulin Adjunct Therapies in Type I Diabetes
This will be a slightly jumbled section because we are describing drugs for the most part
that we do not use in pediatrics. As a matter of fact, most of these drugs are not used in adult
Type I patients but there seems to be some possibility of indications for their use. I was
fascinated by two sessions that I want to report here. The first session occurred on the first day
just before we went to Fenway Park for a Red Sox game. Dr. Kristin Nadeaux from Denver
presented a talk on the role of insulin sensitizers in Type I diabetes. I have known Kristin since
she was a fellow at Barbara Davis Center and have come to respect her tremendously. She
pointed out that macrovascular disease remains a tremendously devastating aspect of diabetes
management. She first quoted some data from the Type I Diabetes Exchange. Over the lasts two
years the average hemoglobin A1c has worsened from 8.2% to 8.4%. She noted it is even worse
in adolescents (9.0%). She noted that this will have a tremendous impact for metabolic memory
down the line. (I mentioned metabolic memory last year in the handout; you may want to go
back and review that.) She reported that severe hypoglycemia remains a tremendous problem in
that 6% of our patients have had an episode of severe hypoglycemia in the past three months. I
am not sure we are seeing that number in our clinic. This compromises care as I have mentioned
in the past. They have a small percentage of patients who are actually meeting the hemoglobin
A1c target. She pointed out that the current focus has all been on insulin delivery. (I plead
guilty to that.) It has led to increased weight gain and more metabolic symptoms. She also
pointed out that insulin resistance (the body not being as sensitive to insulin) predicts
cardiovascular disease. This is due to coronary artery calcification and the mechanisms are not
entirely clear but she stated it is not just obesity. Both youth and adults may have hepatic insulin
resistance regardless of their weight. Again, insulin resistance correlates with mortality,
cardiovascular disease and renal disease. It also is involved in endothelial dysfunction. She
stated that there were no particular markers to enable us to determine insulin resistance (other
than the requirement for larger amounts of larger dose of insulin). It is not related to serum
lipids, leptin levels or adiponectin levels. It also does not correlate with hepatic or visceral fat.
There also is no correlation between insulin resistance and hemoglobin A1c levels.
Mitochondrial function is decreased and it contributes to insulin resistance. Therefore she felt
that treatments aimed at insulin resistance are needed in Type I diabetes but that it is hard to use
these treatments when we do not know the cause. In Type II diabetes, Metformin,
Thiazolidinediones and thyrodonidinezones are used to decrease insulin resistance in the liver
and muscle. Long acting glucagon-like-peptide 1 (GLP-1) which is an Incretin, and pramlintide
have also been used in Type II. Metformin decreases hepatic glucose output and suppresses
gluconeogenesis. It also increases muscle glucose uptake. Unfortunately, in Type I diabetes
there is only short-term improvement. If a patient is studied for three months there is definite
improvement but that is lost at six months and a year. (Some of our patients have seen this when
participating in Metformin studies.) A meta-analysis of studies using Metformin in Type I
diabetes found that there was a decrease in insulin dose of anywhere from 5.5 to 10 units per day,
a decrease in weight and a decrease in total serum cholesterol. There was no increase in
hypoglycemia or DKA. However, a study of 140 obese adolescents with Type I diabetes showed
no significant decrease in hemoglobin A1c at six months. There was a decrease in insulin dose
and a decrease in BMI Z-score (a measurement of obesity) and a decrease percent body fat.
However, only 80% of the patients were tolerating the Metformin at six months since it does
cause abdominal pain and upset. The Thiazolidinediones (TZDs) are rosiglitazone and
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pioglitazone. In Type I diabetes they produce little change in hemoglobin A1c and no significant
change in lipid profiles. However, in poorly controlled Type I patients there was a decrease in
insulin dose. She felt at this time there was little advantage to either of these drugs. I have used
Metformin with some of my patients who are requiring much more insulin than I thought they
should. I have been universally unimpressed to this point. If further drugs become available, it
would be very nice to try them.
Dr. Natish Kuhadiya discussed targeting hyperglycemia in Type I diabetes with
pramlintide, GLP-1 agonists and DPP-4 inhibitors. He noted that amalyn decreases post prandial
hepatic glucose release (this is sugar released from the liver after eating). Amalyn is co-secreted
with insulin and in Type I diabetes the amalyn secretion is deficient. As a matter of fact it is
pretty much a flat line. Pramlintide is a synthetic amalyn that decreases post prandial glucagon
release, thus reducing liver sugar release. It also slows gastric emptying which enables the
absorption of food to more closely mimic the insulin absorption that we currently have with our
subcutaneous insulin delivery. The slower gastric emptying, however, will not last with
subsequent meals but only when the shot is first given. Pramlintide also decreases caloric intake
because it promotes satiety. In various studies the use of Pramlintide has dropped the
hemoglobin A1c anywhere from 0.2 to 0.5%. The amount of insulin is also diminished slightly
although there can be as much as a 50% drop in pre-prandial (the rapid acting that you use)
insulin. There also is documented weight loss and in some studies evidence of both pre- and post
prandial glucose suppression. The problem with Pramlintide is that it must be given as an
injection and cannot be mixed with insulin. Thus we are talking an additional shot each time a
patient eats. The other serious problem is that there is a high incidence of nausea. When patients
use this medication, they must significantly decrease their insulin dose or they will experience
severe hypoglycemia. I had one of my favorite patients use this medication for quite a time and
if I remember correctly, she lowered her insulin at meals by about 50% and sometimes even
more. Liraglutide, a GLP-1 receptor agonist has also been tried in Type I diabetes. He said that
studies have shown that if the hemoglobin A1c is greater than 7.5%, it did not lead to a change in
insulin dose. However, if the patients were better controlled, it did. The liraglutide decreased
glucose excursion without any increase in hypoglycemia. In a study of adult Type I patients the
average serum glucose dropped by 10 mg per day. There was a 0.8% drop in hemoglobin A1c.
The patients found they had more time to target between 70 and 150 mg/dL. There was a 5%
decrease in the time between 150 and 240 mg/dL. As I said, there was no significant change in
hypoglycemia although there was a 1% increase. These patients had a 10% drop in insulin dose.
They also found a decrease of 50 grams of carbohydrate per day in their appetite. It also
improved gastric emptying and has an anti-inflammatory effect. Liraglutide is taken once per
day and the patients felt that there was an improvement in quality of life with its use. Exenatide
decreases post prandial glucose and glucagon release in Type I diabetes. They do have a once
weekly exenatide but I could not find much research on it. It does take a larger bore needle
which I suspect our patients would not like. When used routinely it required one to two
injections per day but as I said there is a formulation available now for once per week. The main
side effect from the drug was nausea. Dr. Julio Rosenstock talked about the potential use of
SGLT-2 inhibitors in Type I diabetes. He emphasized that this drug has not been approved
either by the FDA or the EMA for Type I diabetes. What it does is lowers the renal threshold for
glucose which means that kidneys start spilling more sugar at a lower level than they would
normally do. This increases the amount of sugar in the urine (glycosuria) and lowers serum
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