Ingrid Libman

A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin dependent) diabetes mellitus

SummaryNearly 70 registries from more than 40 countries have collected and published incidence data of childhood Type 1 (insulin-dependent) diabetes mellitus up to the end of the 1980s. The majority of incidence data comes from regions of high incidence i. e. from Europe and North American. All these published data facilitate the descriptive comparison of incidence and variation of the occurrence of Type 1 diabetes roughly throughout the northern hemisphere. The aim of this paper is to review and compare the most recent epidemiology data on the incidence of Type 1 diabetes among children under the age of 15 years. A clear difference in incidence appeared between northern and southern hemisphere with no countries below the equator having an incidence greater than 15.0 per 100,000. In contrast above the equator the disease is common. Between continents the variation in incidence showed that the lowest incidences were found in Asia, followed by Oceania (Australia and New Zealand), South and North America, and the highest rates were in Europe. The incidence varied from 0.6 per 100,000 in Korea and Mexico to 35.3 per 100,000 in Finland showing prominent worldwide variation in incidence of Type 1 diabetes. The largest intracontinental variation in incidence appeared in Europe, varying from the highest in Finland to the lowest (4.6 per 100,000)_in northern Greece. The highest incidence in the world was in northern Europe, but within the continent scale there were some striking exceptions from the overall level of incidence. In Iceland, the northern-most island nation in Europe, the incidence is only one-half of that in Norway and Sweden and one-third of that in Finland. In contrast, in Sardinia in southern Europe the Type 1 diabetes incidence is virtually the same as in Finland, three times higher than overall incidence in Europe. Large variation was also seen in small “pockets” of countries, particularly in the Baltic sea region. The worldwide variation in incidence reflects the distribution of ethnic populations and demonstrates the importance of the differential genetic susceptibility between populations.

Most Youth With Type 1 Diabetes in the T1D Exchange Clinic Registry Do Not Meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes Clinical Guidelines

OBJECTIVE To assess the proportion of youth with type 1 diabetes under the care of pediatric endocrinologists in the United States meeting targets for HbA1c, blood pressure (BP), BMI, and lipids. RESEARCH DESIGN AND METHODS Data were evaluated for 13,316 participants in the T1D Exchange clinic registry younger than 20 years old with type 1 diabetes for ≥1 year. RESULTS American Diabetes Association HbA1c targets of <8.5% for those younger than 6 years, <8.0% for those 6 to younger than 13 years old, and <7.5% for those 13 to younger than 20 years old were met by 64, 43, and 21% of participants, respectively. The majority met targets for BP and lipids, and two-thirds met the BMI goal of <85th percentile. CONCLUSIONS Most children with type 1 diabetes have HbA1c values above target levels. Achieving American Diabetes Association goals remains a significant challenge for the majority of youth in the T1D Exchange registry.

Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: The TODAY clinical trial

OBJECTIVE Among adolescents with type 2 diabetes, there is limited information regarding incidence and progression of hypertension and microalbuminuria. Hypertension and microalbuminuria assessments made during the TODAY clinical trial were analyzed for effect of treatment, glycemic control, sex, and race/ethnicity. RESEARCH DESIGN AND METHODS A cohort of 699 adolescents, 10–17 years of age, <2 years duration of type 2 diabetes, BMI ≥85%, HbA1c ≤8% on metformin therapy, controlled blood pressure (BP), and calculated creatinine clearance >70 mL/min, were randomized to metformin, metformin plus rosiglitazone, or metformin plus intensive lifestyle intervention. Primary study outcome was loss of glycemic control for 6 months or sustained metabolic decompensation requiring insulin. Hypertension and microalbuminuria were managed aggressively with standardized therapy to maintain BP <130/80 or <95th percentile for age, sex, and height and microalbuminuria <30 μg/mg. RESULTS In this cohort, 319 (45.6%) reached primary study outcome, and 11.6% were hypertensive at baseline and 33.8% by end of study (average follow-up 3.9 years). Male sex and higher BMI significantly increased the risk for hypertension. Microalbuminuria was found in 6.3% at baseline and rose to 16.6% by end of study. Diagnosis of microalbuminuria was not significantly different between treatment arms, sex, or race/ethnicity, but higher levels of HbA1c were significantly related to risk of developing microalbuminuria. CONCLUSIONS Prevalence of hypertension and microalbuminuria increased over time among adolescents with type 2 diabetes regardless of diabetes treatment. The greatest risk for hypertension was male sex and higher BMI. The risk for microalbuminuria was more closely related to glycemic control.

Reproducibility of the oral glucose tolerance test in overweight children.

OBJECTIVE We examined the reproducibility of the oral glucose tolerance test (OGTT) in overweight children and evaluated distinguishing characteristics between those with concordant vs. discordant results. DESIGN Sixty overweight youth (8-17 yr old) completed two OGTTs (interval between tests 1-25 d). Insulin sensitivity was assessed by the surrogate measures of fasting glucose to insulin ratio, whole-body insulin sensitivity index, and homeostasis model assessment of insulin resistance, and insulin secretion by the insulinogenic index with calculation of the glucose disposition index (GDI). RESULTS Of the 10 subjects with impaired glucose tolerance (IGT) during the first OGTT only three (30%) had IGT during the second OGTT. The percent positive agreement between the first and second OGTT was low for both impaired fasting glucose and IGT (22.2 and 27.3%, respectively). Fasting blood glucose had higher reproducibility, compared with the 2-h glucose. Youth with discordant OGTTs, compared with those with concordant results, were more insulin resistant (glucose/insulin 2.7+/-1.4 vs. 4.1+/-1.8, P=0.006, whole-body insulin sensitivity index of 1.3+/-0.6 vs. 2.2+/-1.1, P=0.003, and homeostasis model assessment of insulin resistance 10.6+/-8.1 vs. 5.7+/-2.8, P=0.001), had a lower GDI (0.45+/-0.58 vs. 1.02+/-1.0, P=0.03), and had higher low-density lipoprotein cholesterol (117.7+/-36.6 vs. 89.9+/-20.1, P=0.0005) without differences in physical characteristics. CONCLUSIONS Our results show poor reproducibility of the OGTT in obese youth, in particular for the 2-h plasma glucose. Obese youth who have discordant OGTT results are more insulin resistant with higher risk of developing type 2 diabetes mellitus, as evidenced by a lower GDI. The implications of this remain to be determined in clinical and research settings.

Type 2 Diabetes in Childhood: The American Perspective

The incidence of type 2 diabetes mellitus is steadily escalating throughout the world in people from a wide range of ethnic groups and all social and economic levels. Type 2 diabetes is no longer a disease only of adults: parallel with the global epidemic of type 2 diabetes in adults, an ‘emerging epidemic’ of type 2 diabetes has been observed in youth over the last decade. Research and clinical experience in adults have established that insulin resistance is a major risk factor for type 2 diabetes. However, insulin resistance alone is not sufficient to cause diabetes, which will develop only when insulin secretion by the β-cells fails. This review discusses the recent emergence of type 2 diabetes in children and adolescents, its risk factors, pathophysiologic mechanisms and treatment modalities.

Was There an Epidemic of Diabetes in Nonwhite Adolescents in Allegheny County, Pennsylvania?

OBJECTIVE To determine the incidence of IDDM in children aged < 20 years at diagnosis in Allegheny County, Pennsylvania, for the period from 1 January 1990 to 31 December 1994 and to compare the incidence between whites and nonwhites in the same area and for the same time period. RESEARCH DESIGN AND METHODS All new patients diagnosed between January 1990 and December 1994 who were aged < 20 years, on insulin, and residents of Allegheny County at diagnosis were identified from medical records of 23 hospitals in the Allegheny County area. To verify the completeness of the hospitals using the capture-recapture method, pediatricians and diabetologists were used as a secondary source. RESULTS A total number of 257 patients were identified. The overall age-standardized incidence rate was 16.7/100,000. Nonwhites had a slightly higher incidence (17.6/100,000) than whites (16.5/100,000). In the 15–19 years age-group, the incidence in nonwhites (30.4/100,000) was almost three times higher than that in white (11.2/100,000) and more than two times higher than that in the previous period (from 1985 to 1989) (13.8/100,000). CONCLUSIONS For the first time in the Allegheny County registry, and in any other registry, nonwhites showed a higher incidence of IDDM than whites. The high incidence in the 15–19 years age-group was responsible for this phenomenon. This epidemic of diabetes in adolescent nonwhites may be the result of a rising incidence of classical IDDM or another type of diabetes. Further studies using population-based registries are needed to determine whether this increase is being seen in other areas and other ethnic groups and to clarify the reasons for the increase in IDDM among blacks.

Coexistence of type 1 and type 2 diabetes mellitus: “double” diabetes?

Diabetes has been known to medicine for over 2000 yr. Ancient Hindu writings describe people with a mysterious and deadly disease that caused intense thirst, large urine output, and wasting away of the body. An early clue was the attraction of ants and flies to the urine of the victims (1, 2). In the first century AD Arataeus of Cappadocia coined the name ‘diabetes’. The literal translation, ‘to go through’ or siphon, reflects the early understanding of a disease that drained patients of more fluid than they could consume. Later, the Latin word for honey, ‘mellitus’, was appended to diabetes because of its link with sweet urine. Most likely these ancient descriptions related to what we know as type 1 diabetes (T1D) (formerly known as insulin-dependent diabetes) (2). In the 1800s a less symptomatic variant was described, characterized by heavy glycosuria, occurring in later life and associated with obesity rather than wasting. A letter written in 1894 to the Mayor of New York City by Cyrus Edson, the Commissioner of Health, which was published in a popular journal called Overland Monthly and Out West Magazine describes diabetes and its two types as then recognized (3):

Type II diabetes mellitus: no longer just adults.

Type II diabetes mellitus is no longer exclusively a disease of adults. Health care professionals and agencies must gain a better understanding of (1) the epidemiology of type II diabetes mellitus in childhood; (2) the phenotypic, biochemical, metabolic, and autoimmune characteristics at diagnosis and during the course of the disease; (3) therapeutic modalities; (4) screening of high-risk populations; and (5) prevention strategies. This will be one of the challenges in pediatric diabetes as we approach the 21st century.

Prevention and Treatment of Type 2 Diabetes in Youth

Parallel to the increase in obesity worldwide, there has been a rise in the prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents. The etiology of T2DM in youth, similar to adults, is multifactorial including genetic and environmental factors, among them obesity, sedentary lifestyle, family history of the disease, high-risk ethnicity and insulin resistance phenotype playing major roles. Treatment of T2DM should not have a glucocentric approach; it should rather target improving glycemia, dyslipidemia, hypertension, weight management and the prevention of short- and long-term complications. Prevention strategies, especially in high-risk groups, should focus on environmental change involving participation of families, schools, the food and entertainment industries and governmental agencies. Presently, limited pharmacotherapeutic options need to be expanded both for childhood T2DM and obesity. The coming decades will prove very challenging for healthcare providers battling socioeconomic waves conducive to obesity and T2DM. Evidence-based research and clinical experience in pediatrics, possibly modeled after adult trials, need to be developed if this public health threat is to be contained.

Aerobic exercise but not resistance exercise reduces intrahepatic lipid content and visceral fat and improves insulin sensitivity in obese adolescent girls: a randomized controlled trial

It is unclear whether regular exercise alone (no caloric restriction) is a useful strategy to reduce adiposity and obesity-related metabolic risk factors in obese girls. We examined the effects of aerobic (AE) vs. resistance exercise (RE) alone on visceral adipose tissue (VAT), intrahepatic lipid, and insulin sensitivity in obese girls. Forty-four obese adolescent girls (BMI ≥95th percentile, 12-18 yr) with abdominal obesity (waist circumference 106.5 ± 11.1 cm) were randomized to 3 mo of 180 min/wk AE (n = 16) or RE (n = 16) or a nonexercising control group (n = 12). Total fat and VAT were assessed by MRI and intrahepatic lipid by proton magnetic resonance spectroscopy. Intermuscular AT (IMAT) was measured by CT. Insulin sensitivity was evaluated by a 3-h hyperinsulinemic (80 mU·m(2)·min(-1)) euglycemic clamp. Compared with controls (0.13 ± 1.10 kg), body weight did not change (P > 0.1) in the AE (-1.31 ± 1.43 kg) and RE (-0.31 ± 1.38 kg) groups. Despite the absence of weight loss, total body fat (%) and IMAT decreased (P < 0.05) in both exercise groups compared with control. Compared with control, significant (P < 0.05) reductions in VAT (Δ-15.68 ± 7.64 cm(2)) and intrahepatic lipid (Δ-1.70 ± 0.74%) and improvement in insulin sensitivity (Δ0.92 ± 0.27 mg·kg(-1)·min(-1) per μU/ml) were observed in the AE group but not the RE group. Improvements in insulin sensitivity in the AE group were associated with the reductions in total AT mass (r = -0.65, P = 0.02). In obese adolescent girls, AE but not RE is effective in reducing liver fat and visceral adiposity and improving insulin sensitivity independent of weight loss or calorie restriction.