Type 2 Diabetes in Type 2 Diabetes in Children and Children and AdolescentsAdolescents

By: Jennifer HarrisBy: Jennifer Harris

November 17, 2005November 17, 2005

OutlineOutline

Pediatric Obesity – How big is the Pediatric Obesity – How big is the problem, and why should we care?problem, and why should we care?

How does DM2 develop?How does DM2 develop? Clinical Heterogeneity in DM2 – What Clinical Heterogeneity in DM2 – What

are the implications?are the implications? What can we do to stop the What can we do to stop the

epidemic?epidemic? ConclusionsConclusions

Pediatric ObesityPediatric Obesity

How big a problem is pediatric How big a problem is pediatric obesity?obesity?

1999-2002 NHANES (National Health and Nutrition 1999-2002 NHANES (National Health and Nutrition Examination Survey):Examination Survey):

22.6% of 2-5 year olds are “at risk for overweight” 22.6% of 2-5 year olds are “at risk for overweight” (BMI 85-95%)(BMI 85-95%)

31% of 6-19 year olds are “at risk for overweight”31% of 6-19 year olds are “at risk for overweight” 10.3% of 2-5 year olds are “overweight” (BMI 10.3% of 2-5 year olds are “overweight” (BMI

>95%)>95%) 16% of 16-19 year olds are “overweight”16% of 16-19 year olds are “overweight”

This is not just an American trend. Other countries, This is not just an American trend. Other countries, like Japan, New Zealand, and Thailand, are also like Japan, New Zealand, and Thailand, are also seeing increases in childhood development of DM2.seeing increases in childhood development of DM2.

Why should we care?Why should we care?

Annual obesity-related hospital costs in Annual obesity-related hospital costs in 6-17 year olds = $127 million/year, a 6-17 year olds = $127 million/year, a 3-fold increase in the past 20 years 3-fold increase in the past 20 years

Wang and Dietz, Wang and Dietz, PediatricsPediatrics. 109;E81. 109;E81

Metabolic Syndrome in KidsMetabolic Syndrome in Kids

Must have at least 3 to diagnose (in Must have at least 3 to diagnose (in children, all adjusted for age and sex):children, all adjusted for age and sex):

BMI >97th percentileBMI >97th percentile Triglycerides >95th percentileTriglycerides >95th percentile HDL <5th percentileHDL <5th percentile Systolic or diastolic BP >95th percentileSystolic or diastolic BP >95th percentile Impaired glucose tolerance test (IGTT)Impaired glucose tolerance test (IGTT)

The link between obesity, insulin The link between obesity, insulin resistance, and metabolic syndromeresistance, and metabolic syndrome

The prevalence of metabolic syndrome in children increases directly The prevalence of metabolic syndrome in children increases directly with increased insulin resistance. This was seen in Hispanics > with increased insulin resistance. This was seen in Hispanics > Caucasians > African-Americans.Caucasians > African-Americans.

The percentage of children with IGTT increased directly with the The percentage of children with IGTT increased directly with the severity of obesity, even after adjusting for sex, race, and Tanner severity of obesity, even after adjusting for sex, race, and Tanner stage.stage.

The CARDIA study of 4576 young adults showed that there is a The CARDIA study of 4576 young adults showed that there is a weight-independent association between fasting insulin and HTN. weight-independent association between fasting insulin and HTN. (Manolio et al. (Manolio et al. ArteriosclerosisArteriosclerosis. 1990;10:430-36) . 1990;10:430-36)

The AHA released a scientific statement in 2003 stating that The AHA released a scientific statement in 2003 stating that increased LV mass, an independent risk factor for CVD, can already increased LV mass, an independent risk factor for CVD, can already be seen in childhood in obese children. be seen in childhood in obese children.

Weiss, et al. Weiss, et al. NEJMNEJM. 2004;350:2362-74.. 2004;350:2362-74.

How Fatty Acids Interfere with How Fatty Acids Interfere with Insulin-Mediated Glucose Insulin-Mediated Glucose

UptakeUptake

McGarry, J.D. “Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes.” Diabetes. 51:7-18, 2002.

How does DM2 develop?How does DM2 develop?

Factors Contributing to Insulin Factors Contributing to Insulin ResistanceResistance

1. Obesity/sedentary lifestyle1. Obesity/sedentary lifestyle2. Race/ethnicity2. Race/ethnicity3. Family history3. Family history

a. The Bogalusa Heart Study (Srinivasan, et al. a. The Bogalusa Heart Study (Srinivasan, et al. MetabolismMetabolism. 2003; 52:443-450.) looked at >6500 . 2003; 52:443-450.) looked at >6500 kids age 4-17, with and without parental DM, from kids age 4-17, with and without parental DM, from childhood to adulthood.childhood to adulthood.b. In kids with parental DM:b. In kids with parental DM:

1. Increased BMI and SBP starting in 1. Increased BMI and SBP starting in childhood.childhood.

2. Increased fasting insulin, glucose, and 2. Increased fasting insulin, glucose, and insulin insulin resistance index starting in puberty.resistance index starting in puberty.

3. Increased TGs and LDL, decreased HDL 3. Increased TGs and LDL, decreased HDL starting starting in adulthood.in adulthood.

Factors (Factors (continuedcontinued))4. Puberty: increased GH/IGF-1 levels cause insulin 4. Puberty: increased GH/IGF-1 levels cause insulin

resistanceresistance

a. Insulin-mediated glucose disposal decreased 30% a. Insulin-mediated glucose disposal decreased 30% in Tanner Stages 2-4 compared to Stage 1 in some in Tanner Stages 2-4 compared to Stage 1 in some hyperinsulinemic euglycemic clamp studies. hyperinsulinemic euglycemic clamp studies.

b. Caprio et al. (b. Caprio et al. (Journal of PediatricsJournal of Pediatrics. June 1989: 963-. June 1989: 963-967) showed, via a hyperglycemic clamp study, that 967) showed, via a hyperglycemic clamp study, that both early and late responses to hyperglycemia were both early and late responses to hyperglycemia were enhanced during puberty (leading to enhanced during puberty (leading to hyperinsulinemia). This differs from the hyperinsulinemia). This differs from the hyperinsulinemia seen in early DM2, where the early hyperinsulinemia seen in early DM2, where the early phase release of insulin is impaired, and late phases phase release of insulin is impaired, and late phases exhibit a compensatory increased insulin release.exhibit a compensatory increased insulin release.

Factors (continued)Factors (continued)

5. PCOS5. PCOS

6. Intrauterine factors (GDM, low birth weight, small 6. Intrauterine factors (GDM, low birth weight, small head circumference)head circumference)a. A study in Pima Indians showed that a. A study in Pima Indians showed that intrauterine factors were separate from family intrauterine factors were separate from family history. Kids born after mom developed DM2 history. Kids born after mom developed DM2 were more likely to get DM than siblings born were more likely to get DM than siblings born before mom developed DM2. (Pettitt, et al. before mom developed DM2. (Pettitt, et al. Diabetes CareDiabetes Care. 1993;16:310-14). 1993;16:310-14)b. LBW: thrifty gene hypothesis. Associated with b. LBW: thrifty gene hypothesis. Associated with increased fasting insulin and decreased beta cell increased fasting insulin and decreased beta cell function.function.

How DM2 develops – How DM2 develops – traditional thinkingtraditional thinking

Insulin resistance Insulin resistance pancreatic insulin pancreatic insulin secretion increases secretion increases beta cell failure beta cell failure decompensation decompensation clinical DM. clinical DM.

This way of thinking may This way of thinking may underemphasize the role of beta cell underemphasize the role of beta cell dysfunction.dysfunction.

A new paradigmA new paradigm

There is some evidence that there is beta There is some evidence that there is beta cell dysfunction present before the onset cell dysfunction present before the onset of impaired glucose tolerance. of impaired glucose tolerance.

It is important to note that just because It is important to note that just because insulin secretion increases in the early insulin secretion increases in the early stages of DM2, this doesn’t necessarily stages of DM2, this doesn’t necessarily mean the beta cells are functioning mean the beta cells are functioning properly. Late hyperinsulinemia may in properly. Late hyperinsulinemia may in fact be a result of inadequate beta cell fact be a result of inadequate beta cell response to hyperglycemia that is itself a response to hyperglycemia that is itself a result of early impaired insulin release.result of early impaired insulin release.

Gerich, J.E. Gerich, J.E. Endocrine ReviewsEndocrine Reviews. 1998;19(4): 491-503.. 1998;19(4): 491-503.

Clinical Heterogeneity in Clinical Heterogeneity in DM2DM2

What do all DM2 patients have What do all DM2 patients have in common?in common?

Both genetic and environmental components are involved.Both genetic and environmental components are involved.

Has polygenic inheritance.Has polygenic inheritance.1. Diabetogenic genes: Genes that, if inherited, will cause 1. Diabetogenic genes: Genes that, if inherited, will cause most people to develop DM. Essential and specific to the most people to develop DM. Essential and specific to the development of DM, but may not be enough by themselves to development of DM, but may not be enough by themselves to cause DM. Example: mutation in insulin receptor gene that cause DM. Example: mutation in insulin receptor gene that leads to insulin resistance.leads to insulin resistance.2. Diabetes-related genes: Not specific. By themselves, not 2. Diabetes-related genes: Not specific. By themselves, not enough to cause DM. Genetically-determined risk factors. enough to cause DM. Genetically-determined risk factors. Example: genes that regulate appetite and energy Example: genes that regulate appetite and energy expenditure.expenditure.

Both insulin sensitivity and insulin secretion are impaired.Both insulin sensitivity and insulin secretion are impaired.

Most patients are obese. Obesity, especially intra-abdominal, Most patients are obese. Obesity, especially intra-abdominal, is believed to cause insulin resistance.is believed to cause insulin resistance.

Differentiating DM1 from DM2Differentiating DM1 from DM2(Not always as easy as it may seem!)(Not always as easy as it may seem!)

DM1DM11. Increased incidence of other autoimmune disorders1. Increased incidence of other autoimmune disorders2. Ususally low insulin/c-peptide levels (may be normal during 2. Ususally low insulin/c-peptide levels (may be normal during

“honeymoon phase”)“honeymoon phase”)3. Usually non-obese3. Usually non-obese

DM2DM21. Increased c-peptide levels (may be normal at time of diagnosis)1. Increased c-peptide levels (may be normal at time of diagnosis)2. Usually no auto-antibodies (can sometimes see these, however, 2. Usually no auto-antibodies (can sometimes see these, however,

and this is usually prognostic for a more severe clinical and this is usually prognostic for a more severe clinical picture/rapid progression)picture/rapid progression)

3. Strong family history of diabetes3. Strong family history of diabetes4. Usually obese4. Usually obese5. Signs of insulin resistance (HTN, acanthosis, PCOS)5. Signs of insulin resistance (HTN, acanthosis, PCOS)

Acanthosis nigricansAcanthosis nigricans

Currently thought to be an effect of IGF-1. At one point was Currently thought to be an effect of IGF-1. At one point was thought to be a result of skin folds rubbing together.thought to be a result of skin folds rubbing together.

One study cited in One study cited in The Journal of PediatricsThe Journal of Pediatrics (2001;138:453-4) (2001;138:453-4) showed acanthosis was directly associated with:showed acanthosis was directly associated with:1. Increased fasting insulin levels1. Increased fasting insulin levels2. Increased insulin/glucose ratio2. Increased insulin/glucose ratio3. Increased insulin responses and decreased glucose 3. Increased insulin responses and decreased glucose disposal rates during hyperglycemic clampsdisposal rates during hyperglycemic clamps4. These effects seen in patients with acanthosis more than 4. These effects seen in patients with acanthosis more than in overweight patients without acanthosis. (However, after in overweight patients without acanthosis. (However, after adjusting for differences in total body fat, there was no adjusting for differences in total body fat, there was no significant difference between overweight patients with and significant difference between overweight patients with and without acanthosis.)without acanthosis.)

How does DM2 differ from How does DM2 differ from patient to patient?patient to patient?

Not all people with DM2 are insulin resistant. Not all people with DM2 are insulin resistant. Several studies (cited in Gerich, J.E. Several studies (cited in Gerich, J.E. Endocrine Endocrine ReviewsReviews. 1998;19(4): 491-503), demonstrate that . 1998;19(4): 491-503), demonstrate that certain subgroups of type 2 diabetics have certain subgroups of type 2 diabetics have impaired insulin secretion, but not insulin impaired insulin secretion, but not insulin resistance. So why wouldn’t you call these resistance. So why wouldn’t you call these patients type 1? Because they are not ketosis-patients type 1? Because they are not ketosis-prone and won’t die without insulin.prone and won’t die without insulin.

Compensatory responses to insulin resistance are Compensatory responses to insulin resistance are different in different ethnic groups.different in different ethnic groups.1. AA: decreased hepatic extraction of insulin1. AA: decreased hepatic extraction of insulin2. Hispanic: increased 2nd phase secretion of 2. Hispanic: increased 2nd phase secretion of insulininsulin

How does DM2 differ from How does DM2 differ from patient to patient? (continued)patient to patient? (continued)

HHNK (hyperglycemic hyperosmolar non-ketosis) is HHNK (hyperglycemic hyperosmolar non-ketosis) is a common presentation of DM2 in kids. Fourtner, a common presentation of DM2 in kids. Fourtner, et al. (et al. (Pediatric DiabetesPediatric Diabetes. 2005;6:129-135) . 2005;6:129-135) conducted a chart review at CHOP, and found conducted a chart review at CHOP, and found that 7/190 patients diagnosed with DM2 that 7/190 patients diagnosed with DM2 presented with HHNK, one of whom subsequently presented with HHNK, one of whom subsequently died. HHNK doesn’t seem to be associated with died. HHNK doesn’t seem to be associated with concurrent infections/stresses like commonly concurrent infections/stresses like commonly seen in adult HHNK.seen in adult HHNK.

African American children appear to be more likely African American children appear to be more likely to present in DKA than other races/ethnicities, for to present in DKA than other races/ethnicities, for reasons not fully understood. reasons not fully understood.

How does DM2 differ from How does DM2 differ from patient to patient? (continued)patient to patient? (continued)

MODY (maturity-onset diabetes of the young)MODY (maturity-onset diabetes of the young) An AD-inherited, heterogeneous group of disorders.An AD-inherited, heterogeneous group of disorders. Characterized by:Characterized by:

1. nonketotic DM1. nonketotic DM2. onset usually <25 years old2. onset usually <25 years old3. primary defect of beta cell function3. primary defect of beta cell function4. at least 6 different genes have been implicated4. at least 6 different genes have been implicated5. can be affected/precipitated by factors affecting insulin 5. can be affected/precipitated by factors affecting insulin sensitivity (puberty, pregnancy, infection)sensitivity (puberty, pregnancy, infection)

Typical presentation: Mild, asymptomatic hyperglycemia in Typical presentation: Mild, asymptomatic hyperglycemia in nonobese young person with prominent family history of nonobese young person with prominent family history of diabetes.diabetes.

May account for up to 5% of all DM in the US and other May account for up to 5% of all DM in the US and other industrialized countries.industrialized countries.

Similar to DM2 in that beta cell experiences a decline in Similar to DM2 in that beta cell experiences a decline in function.function.

Case PresentationCase Presentation(from Gassner, et al. (from Gassner, et al. Clinical DiabetesClinical Diabetes. 2003; 21,3, 140-1). 2003; 21,3, 140-1)

17 YO AAF with new-onset DM. 17 YO AAF with new-onset DM. History and PhysicalHistory and Physical

HPI: polyuria, polydipsia, weight lossHPI: polyuria, polydipsia, weight lossFH: + family history of DM, no family history of autoimmune FH: + family history of DM, no family history of autoimmune diseasesdiseasesVS: 103/53, 79, 37CVS: 103/53, 79, 37CWeight=60kg, height=61in; BMI=25 (85th percentile)Weight=60kg, height=61in; BMI=25 (85th percentile)PE: + acanthosis, Tanner stage 5PE: + acanthosis, Tanner stage 5

Labs:Labs:UA: glucose >1000 mg/dl, ketones=40 mg/dlUA: glucose >1000 mg/dl, ketones=40 mg/dlSerum glucose=726, bicarbonate=21, venous pH=7.37 Serum glucose=726, bicarbonate=21, venous pH=7.37 A1C=8.6%, c-peptide=1.0 ng/ml (nl=0.6-3.2)A1C=8.6%, c-peptide=1.0 ng/ml (nl=0.6-3.2)

Type 1 or Type 2??Type 1 or Type 2??

Case Presentation Case Presentation (continued)(continued)

She was admitted, given insulin and fluids, and She was admitted, given insulin and fluids, and diagnosed with Type 2 DM based on her race, diagnosed with Type 2 DM based on her race, family history, acanthosis, elevated BMI, normal family history, acanthosis, elevated BMI, normal c-peptide level, and lack of ketoacidosis.c-peptide level, and lack of ketoacidosis.

She was started on metformin and insulin, and She was started on metformin and insulin, and counseled about a diabetic diet.counseled about a diabetic diet.

However, at her 1 month follow-up visit, her labs However, at her 1 month follow-up visit, her labs came back positive for islet cell antibodies (ICAs), came back positive for islet cell antibodies (ICAs), glutamic acid decarboxylase (GAD) antibodies, glutamic acid decarboxylase (GAD) antibodies, and ICA-512 antibodies.and ICA-512 antibodies.

Her A1C had decreased at this point, and her Her A1C had decreased at this point, and her glucose was WNL on 0.4u/kg/day of insulin. glucose was WNL on 0.4u/kg/day of insulin. Metformin was stopped given the patient’s Metformin was stopped given the patient’s antibody status.antibody status.

““Double Diabetes” or “Type 1.5 Double Diabetes” or “Type 1.5 DM”DM”

This patient represents a type of DM in which the patient This patient represents a type of DM in which the patient has characteristics of both Type 1 and Type 2.has characteristics of both Type 1 and Type 2.

As of 2003, there were tests for 4 different antibodies As of 2003, there were tests for 4 different antibodies commercially available. 90% of DM1 patients will test commercially available. 90% of DM1 patients will test positive for at least 1 antibody, and 40-50% will test positive for at least 1 antibody, and 40-50% will test positive for 2 or more.positive for 2 or more.

Interestingly, AA adolescents with DM1 are four times more Interestingly, AA adolescents with DM1 are four times more likely to have no antibodies at time of diagnosis.likely to have no antibodies at time of diagnosis.

This is dangerous, because if you had assumed that this This is dangerous, because if you had assumed that this patient was DM2 without sending antibody tests, you might patient was DM2 without sending antibody tests, you might have sent her home on metformin only. Then, when the have sent her home on metformin only. Then, when the honeymoon period was over, she could decompensate and honeymoon period was over, she could decompensate and end up in DKA.end up in DKA.

Moral of the story: Moral of the story: AlwaysAlways send antibody tests in children send antibody tests in children and adolescents, no matter how clear-cut you think the and adolescents, no matter how clear-cut you think the diagnosis is!diagnosis is!

What can we do to stop the What can we do to stop the epidemic?epidemic?

Current Treatment Current Treatment RecommendationsRecommendations

Per American Academy of Pediatrics:Per American Academy of Pediatrics:1. Glucose 126-200 and A1C <8.5 1. Glucose 126-200 and A1C <8.5 lifestyle modifications +/- lifestyle modifications +/- metforminmetformin2. Glucose >200 and A1C >8.5, +/- ketosis 2. Glucose >200 and A1C >8.5, +/- ketosis insulin insulin3. Do NOT give metformin if patient is ketotic, because this 3. Do NOT give metformin if patient is ketotic, because this increases the risk of lactic acidosis.increases the risk of lactic acidosis.

Per ADA:Per ADA:1. Start with diet and exercise.1. Start with diet and exercise.2. If goals not met, start monotherapy (usually metformin).2. If goals not met, start monotherapy (usually metformin).3. If goals still not met, add a second oral agent (sulfonylurea, 3. If goals still not met, add a second oral agent (sulfonylurea, meglitinide, or a TZD).meglitinide, or a TZD).4. If goals still not met, start insulin. You should start insulin 4. If goals still not met, start insulin. You should start insulin immediately if the patient presents with DKA.immediately if the patient presents with DKA.

Metformin is currently the only oral hypoglycemic that has been Metformin is currently the only oral hypoglycemic that has been approved for use in children.approved for use in children.

Lifestyle ModificationsLifestyle Modifications Lifestyle modifications are most efficacious, but Lifestyle modifications are most efficacious, but

metformin decreases rate of progression to DM.metformin decreases rate of progression to DM.

Robinson (Robinson (JAMAJAMA. 1999;282:1561-1567) started a 6 . 1999;282:1561-1567) started a 6 month curriculum in 3rd and 4th graders in San month curriculum in 3rd and 4th graders in San Jose, CA to see what effect decreasing TV Jose, CA to see what effect decreasing TV watching/video games would have on obesity, and watching/video games would have on obesity, and found that there was a significant decrease in BMI, found that there was a significant decrease in BMI, triceps skinfold thickness, waist circumference, and triceps skinfold thickness, waist circumference, and waist-hip ratio.waist-hip ratio.

Programs to eliminate coke and candy machines Programs to eliminate coke and candy machines from schools and serve healthier lunches are in from schools and serve healthier lunches are in place now throughout the country, but how place now throughout the country, but how efficacious are these?efficacious are these?

Role of insulinRole of insulin

Early insulin therapy in adults is thought Early insulin therapy in adults is thought to possibly reverse some of the to possibly reverse some of the glucotoxicity that damages beta cells glucotoxicity that damages beta cells and other insulin-sensitive tissues.and other insulin-sensitive tissues.

There is some evidence suggesting that There is some evidence suggesting that DM2 may be more aggressive in young DM2 may be more aggressive in young people, so early insulin therapy should people, so early insulin therapy should be strongly considered.be strongly considered.

Upcoming TrialsUpcoming TrialsThere are trials currently looking at rosiglitazone, meglitinide, There are trials currently looking at rosiglitazone, meglitinide,

and glucovance in kids. One example is the STOPP-T2D and glucovance in kids. One example is the STOPP-T2D trial (Studies to Treat of Prevent Pediatric Type 2 Diabetes), trial (Studies to Treat of Prevent Pediatric Type 2 Diabetes), sponsored by National Institutes of Diabetes, Digestive, and sponsored by National Institutes of Diabetes, Digestive, and Kidney DiseasesKidney Diseases

Kids with diagnosis for <2 years are randomized to one of 3 Kids with diagnosis for <2 years are randomized to one of 3

arms:arms:1. Metformin1. Metformin2. Metformin + Rosiglitazone2. Metformin + Rosiglitazone3. Metformin + intensive lifestyle program3. Metformin + intensive lifestyle program

Failure = A1C >8% for 6 months Failure = A1C >8% for 6 months start glargine insulin start glargine insulinSecondary outcomes to be studied: beta cell function, insulin Secondary outcomes to be studied: beta cell function, insulin

resistance, body composition, nutrition, physical resistance, body composition, nutrition, physical activity/fitness, CV risk factors, microvascular activity/fitness, CV risk factors, microvascular complications, quality of life, and psychological outcomes.complications, quality of life, and psychological outcomes.

Bariatric Surgery in Children Bariatric Surgery in Children and Adolescents (continued)and Adolescents (continued)

Guidelines from American Pediatric Surgery Association Guidelines from American Pediatric Surgery Association Clinical Task Force on Bariatric Surgery:Clinical Task Force on Bariatric Surgery:

Failure to lose weight after 6 months of organized attempts.Failure to lose weight after 6 months of organized attempts. Near-mature physiologic status of Tanner Stage 3 or above.Near-mature physiologic status of Tanner Stage 3 or above. BMI >/= 40 with major life-threatening comorbidities or >/= BMI >/= 40 with major life-threatening comorbidities or >/=

50 with minor but life-altering comorbidities.50 with minor but life-altering comorbidities. Commitment to medical and psychological evaluation pre Commitment to medical and psychological evaluation pre

and post-op.and post-op. Commitment to avoid pregnancy for at least 1 year post-op.Commitment to avoid pregnancy for at least 1 year post-op. Ability and intent to adhere to post-op nutritional guidelines.Ability and intent to adhere to post-op nutritional guidelines. Supportive family environment.Supportive family environment. Ability to provide informed assent (patient) and consent Ability to provide informed assent (patient) and consent

(family).(family).

Bariatric Surgery in Children Bariatric Surgery in Children and Adolescentsand Adolescents

Potential complications:Potential complications: Interference with linear growthInterference with linear growth Ethics of informed consentEthics of informed consent Not enough data available about future Not enough data available about future

reproductive capabilityreproductive capability Increased impact of decreased nutrient Increased impact of decreased nutrient

absorption when patient is still growingabsorption when patient is still growing

Bottom line: Long term effects on Bottom line: Long term effects on adolescents not known.adolescents not known.

ConclusionsConclusions The more we learn about DM, the more is appears to The more we learn about DM, the more is appears to

be a continuum of disorders, evidenced by how hard be a continuum of disorders, evidenced by how hard it is sometimes to differentiate type 1 and type 2. it is sometimes to differentiate type 1 and type 2. Also evidenced by the variety of clinical pictures, Also evidenced by the variety of clinical pictures, and subtle laboratory nuances when mechanisms and subtle laboratory nuances when mechanisms are studied.are studied.

Children developing DM2 may help us understand Children developing DM2 may help us understand how this continuum works, and may help us explore how this continuum works, and may help us explore some of the genetic differences that result in the some of the genetic differences that result in the spectrum of disorders that are classified as diabetes.spectrum of disorders that are classified as diabetes.

Knowing these subtle differences in mechanism, and Knowing these subtle differences in mechanism, and knowing how to test patients for which knowing how to test patients for which mechanism(s) are causing their DM, may help us mechanism(s) are causing their DM, may help us eventually tailor treatment programs on an eventually tailor treatment programs on an individual basis.individual basis.

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Gassner, HL, and Gitelman, SE. “Case Study: Type 1 and Type 2, Too?” Gassner, HL, and Gitelman, SE. “Case Study: Type 1 and Type 2, Too?” Clinical DiabetesClinical Diabetes. . 2003;21(3):140-1.2003;21(3):140-1.

Thank You!Thank You!

Dr. Frank Franklin, UABDr. Frank Franklin, UAB

Dr. Amy Potter, VanderbiltDr. Amy Potter, Vanderbilt