Objective. To describe the characteristics of youth-onset noninsulin-dependent diabetes mellitus (NIDDM) at diagnosis and compare them with youths with insulin-dependent diabetes mellitus (IDDM) when matched for age, sex, and geographic region of residence.
Study Design. Medical records of youths referred for evaluation of diabetes to a pediatric tertiary care center from 1988 to 1995 were reviewed to identify youths diagnosed with NIDDM. Patients selected for study met National Diabetes Data Group criteria for type of diabetes.
Results. Fifty patients with NIDDM were reviewed and compared with similar IDDM patients. The NIDDM female:male ratio was 1.6:1 and 74% were African-American. Only 18% of the IDDM patients were African-American. The mean body mass index ± standard error at diagnosis of NIDDM patients was 35 ± 1.1 kg/m2 in contrast to IDDM, 20 ± .8 kg/m2. Ninety-six percent of NIDDM and 24% of IDDM youths had a body mass index ≥85th percentile. More then 30% of NIDDM youths presented with hypertension. Diabetic ketoacidosis was present in >25% of NIDDM patients. Acanthosis nigricans was documented in 86% of NIDDM and 0% of IDDM patients.
Conclusions. In Arkansas, youths with NIDDM are characterized by significant obesity in contrast to youths with IDDM. Physical charcteristics such as obesity, acanthosis nigricans, and hypertension on examination of any youth with new-onset diabetes should raise suspicison of NIDDM.
Until recently, noninsulin-dependent diabetes mellitus (NIDDM) had not been considered a pediatric disease. Traditionally, NIDDM has been believed to be an adult disease entity with known risk factors of obesity, sedentary lifestyle, and positive family history.1-4 NIDDM has been extensively studied and well classified in adults.3,5-8 An association with obesity, hyperinsulinism, and the progressive transition from glucose intolerance to clinical diabetes is well documented.3,7-12A rare subtype of NIDDM, maturity onset diabetes of youth (MODY), represents patients with NIDDM who clearly inherit their diabetes in an autosomal dominant manner.13 This condition has been recognized since the 1960s.13 Age at diagnosis typically is less than 21 years of age.14 Some MODY patients have been linked to one of three gene loci.3 Defects in insulin secretion,15-17 number and affinity of insulin receptors,17 and glucagon excess16 have been linked to MODY.
Few studies of youths with NIDDM have been published. A recent population-based study performed in the greater Cincinnati area was undertaken to determine the incidence of NIDDM in youths and if it had changed over time.18 In this study, a 10-fold increase in incidence of NIDDM was reported over a 13-year period. A significant association of NIDDM and obesity was described; 92% of these youths had a body mass index (BMI) more than the 90th percentile.18
Multiple classifications for diabetes have been used in the past resulting in confusing terminology. Much discussion is present in the literature regarding this issue, including the suggestion that a simplified system of names be adopted based on physiologic insulin production.19 For this study, terms defined by the National Diabetes Data Group of the National Institutes of Health and the World Health Organization Expert Committee on Diabetes will be used.1,2,5,20 The National Diabetes Data Group and the World Health Organization Expert Committee on Diabetes have defined the following criteria for the diagnosis of NIDDM.1,2,5,20Insulin levels may be normal, elevated, or depressed; hyperinsulinemia and insulin resistance characterize most patients; not insulin-dependent or ketosis-prone under normal circumstances, but may use insulin for treatment of hyperglycemia; onset may occur at any age, but predominantly onset is after age 40; approximately 50% of men and 70% of women are obese.1,2,5,20 Youth-onset NIDDM has been used in this study to describe individuals less than 21 years of age who meet the criteria for NIDDM as outlined above.
At initial presentation it is sometimes difficult to discern the correct etiology of new-onset diabetes, particularly when evaluating children and adolescents.21,22 The following case is presented to illustrate the diagnostic dilemmas which face the clinician when evaluating the patient with new-onset diabetes.
A 13-year-old black female presented to a local Emergency Department after “talking crazy” for approximately 24 hours which progressed to lethargy and intermittent unconsciousness. Her parents reported that the youth had experienced difficulty breathing and chest pain for several days before changes in her mental status. Further history disclosed prolonged polydipsia, polyuria, and nocturia. Physical examination revealed an obese female with lethargy and altered consciousness, Kussmaul respirations, and prolonged capillary refill. Her blood pressure was 150/100 mm Hg, weight was 128.5 kg, and BMI was 54 kg/m2 (50th percentile BMI for age = 19.2 kg/m2).23 Her initial laboratory evaluation confirmed diabetic ketoacidosis (DKA) with blood glucose 780 mg/dL (43.3 mmol/L), carbon dioxide (CO2) < 5 meq/L (mmol/L), moderate serum ketones, and a large amount of glucose in the urine. After volume expansion with 2 liters of normal saline, consciousness improved. Despite remaining somewhat confused, the patient complained of severe chest pain. Chest roentgenography demonstrated a pneumomediastinum. After stabilization, she was transferred to our facility. The patient's DKA resolved only after 60 hours of standard DKA therapy, including intravenous insulin infusion at .1 units/kg/hour and rehydration. As the ketoacidosis and hyperglycemia improved, glucose tolerance also improved significantly. Insulin therapy was discontinued after 5 days and the patient was discharged on glipizide 5 mg/day. She has remained on this oral hypoglycemic agent for 3 years with adequate glucose control. Her HbA1C was 10.6% (3.4 to 6.1) and a fasting C-peptide was 2.2 ng/mL (mg/L) (normal, .4 to 2.4 ng/mL [mg/L]) at diagnosis.
The patient in the case presentation was morbidly obese and had evidence of normal insulin production as demonstrated by a normal C-peptide of 2.2 ng/mL (mg/L) (normal, .4 to 2.4 ng/mL [mg/L]). After resolution of the patient's DKA, marked improvement of glucose tolerance was observed. No episodes of ketosis have been reported since insulin therapy was discontinued. Patients similar to the case above have been reported by Umpierezz et al,24 who found that 15% of African-Americans presenting with DKA are obese, and Banjeri et al25 who documented black adults with NIDDM presenting in DKA. No evidence of autoimmune b cell destruction was found in the patients of either study. Seventy percent of the obese patients reported by Umpierrez et al24 followed a clinical course similar to that of our patient.
In contrast to other studies which have addressed the increased incidence of youth-onset NIDDM, the objective of this study was to discern which, if any, clinical characteristics at diagnosis are most useful in distinguishing between youths with NIDDM and insulin-dependent diabetes mellitus (IDDM).
MATERIALS AND METHODS
A retrospective chart review of youths previously diagnosed with NIDDM and IDDM was undertaken to assess their characteristics at the time of diagnosis. A total of 50 youths were selected for the NIDDM group and a comparison group of youths with IDDM were matched based on sex, age at diagnosis (within 3 years), and geographic region of residence. Data were collected in four major categories during the chart review: 1) Demographics and history, including routine sociodemographics, date and age at diagnosis of diabetes, past medical history, and family history; 2) Symptoms of diabetes such as polyuria, polydipsia, nocturia, visual complaints, weight loss, dizziness, polyphagia, and fatigue; 3) Physical characteristics assessed at the time of diagnosis including height, weight, blood pressure, acanthosis nigricans, and hirsutism; and 4) Biochemical markers of pancreatic function, glucose tolerance, and electrolyte balance. Medical records of patients referred to the Division of Pediatric Endocrinology at Arkansas Children's Hospital, University of Arkansas for Medical Sciences, were reviewed for evaluation of diabetes. Patients diagnosed with diabetes over an 8-year period between January 1988 and December 1995 were evaluated for the study. If a patient had previously been diagnosed with NIDDM, their diagnostic evaluation was compared with World Health Organization and National Diabetes Data Group criteria to insure appropriate patient selection.1,2,5,20 Patients with the diagnosis of NIDDM, but insufficient or absent data to confirm the diagnosis, were excluded from the study. Approval for this study was obtained from the University of Arkansas for Medical Sciences Human Research Advisory Committee.
Statistical analysis of the various data compared the patients with NIDDM and IDDM. Because of the small size of the data set, Fisher's exact test was used to provide percentage comparisons rather than χ2 analysis. Continuous characteristics were compared using the Student's t test for the various characteristics of interest. All tests were two sided and P values < .05 were deemed statistically significant. Data are described in terms of percentages or means ± standard error of the mean.
The results of the study will be grouped into the four categories: 1) demographics and history, 2) symptoms, 3) physical findings, and 4) biochemical markers.
Demographics and History
Since 1991, the number of patients diagnosed with new-onset NIDDM has steadily risen at Arkansas Children's Hospital. Figure1 shows the increase in patients by year of diagnosis, peaking in 1995 with 34%, or 17 of the 50 NIDDM patients. Of the NIDDM patients, 62% were female and 38% male for an overall female:male ratio of 1.6:1. Sex distribution was similar for the IDDM group because sex was an inclusion criterion. The majority of the NIDDM patients, 74%, were African-American. Of the remainder, 2% were Hispanic and 24% white. Of the IDDM patients, 18% were African-American and 82% white. The ethnic distribution is illustrated in Fig 2. Arkansas's ethnic distribution was estimated at 82% white and 16% African-American in the 1990 Census.26 The mean age at diagnosis for individuals with NIDDM was 13.9 ± .4 years with a range from 8 to 19 years.
Review of past medical histories revealed no significant differences in the number of patients with asthma, heart disease, kidney disease, or substance abuse. However, mental retardation was noted in the medical history of 12% of NIDDM patients and 0% of IDDM patients (P = .03). Insufficient data were recorded in the medical records to accurately assess family history of diabetes in either group.
At the time of diagnosis, symptoms commonly associated with the initial presentation of diabetes were compared between the patients with NIDDM and IDDM. Abdominal pain, headache, nocturia, polydipsia, polyphagia, polyuria, dizziness, and visual disturbance were reported with similar frequency from both groups. Only weight loss was observed to be significantly different. Forty percent of NIDDM patients reported weight loss at diagnosis compared with 70% of IDDM patients (P = .005). Table 1 summarizes the symptoms associated with the presentation of diabetes in youths with NIDDM and IDDM.
Physical characteristics including BMI, blood pressure, and acanthosis nigricans were assessed from data collected at diagnosis. Figure 3 shows the differences between NIDDM and IDDM for these characteristics. BMIs (kg/m2) were calculated from data obtained from chart review and adjusted for sex and race.23 BMI ≥85th percentile for age is generally accepted to represent obesity, including the pediatric population. Using BMI ≥85th percentile, 96% of the NIDDM and 24% of the IDDM study patients were obese (P < .001). For BMI ≥95th percentile for age, 85% of NIDDM and 11% of IDDM were in the superobese category (P < .001). Mean weight at diagnosis for all patients with NIDDM was 92 ± 4 kg and for all patients with IDDM, 49 ± 2 kg (P < .001).
When age at diagnosis was compared with BMI at diagnosis, at all ages of presentation, NIDDM patients, both male and female, were found to be obese. This finding is illustrated in Fig 4. Additionally, there was an upward trend in BMI as age at diagnosis increased. Mean BMI for all IDDM patients was 20 ± .8 kg/m2 and for all NIDDM patients 35 ± 1.1 kg/m2 (P < .001). There was no significant difference between male and female BMI for either group.
Hypertension was reported in 32% of NIDDM and 4% of IDDM youths (P = .001). Systolic and diastolic blood pressures were significantly different between NIDDM and IDDM patients. Mean systolic and diastolic blood pressures for patients with NIDDM were 131 and 82 mmHg, respectively, and for patients with IDDM were 114 and 72 mmHg, respectively (P < .001). Acanthosis nigricans was observed in 86% of youths with NIDDM but was not observed in any patient with IDDM (P < .001).
Biochemical characteristics measured most frequently in both groups included HbA1C, initial blood glucose, CO2, serum ketones, and urine ketones. HbA1C was similar in both groups, 11.0 ± .6% for the NIDDM group and 11.0 ± .5% for the IDDM group. Initial blood glucose concentration differed significantly between the two groups with the NIDDM patients of 339 ± 23 mg/dL (18.8 ± 1.3 mmol/L) and the IDDM patients of 554 ± 50 mg/dL (30.8 ± 2.8 mmol/L), (P < .001). Measures of ketoacidosis revealed less significant differences between the two groups, reported as NIDDM versus IDDM: CO2 (21 ± 1 mEq/L [mmol/L] vs 18 ± 1 mEq/L [mmol/L], P = .01), serum ketones measuring moderate to large (16% vs 36%,P = .07), and urine ketones measuring moderate to large (18% vs 56%, P < .001).
Insulin and C-peptide concentrations measured at diagnosis were significantly elevated in patients with NIDDM. Mean insulin concentration for the NIDDM patients was 108 ± 40 mU/mL (775 ± 28 pmol/L) compared with the insulin concentration of IDDM patients of 12 ± 5 mU/mL (86 ± 35 pmol/L), (normal, 0 to 20 mU/mL [35 to 145 pmol/L]); (P = .02). C-peptide concentration for patients with NIDDM was 4 ± 1.0 ng/mL (mg/L) and for patients with IDDM .8 ± .2 ng/mL (mg/L)(normal, .4 to 3.4 ng/mL [mg/L]); (P = .02). Only 55 of the entire 100 study participants had insulin or C-peptide concentrations obtained. However, obese patients were 4.6 times more likely to have had either a C-peptide or insulin level obtained at diagnosis than their lean counterparts with diabetes. Results of biochemical characteristics are summarized in Table 2.
Islet cell antibodies (ICA) measurement was initiated in new-onset diabetes in 1994 at our institution. However, difficulty with the quality of the commercial assay was encountered resulting in no positive samples in one year. Consequently, the results of the assay have been excluded from this study. Since changing to a research based laboratory, markers of autoimmunity (ICA and/or glutamic acid decarboxylase) have been present in approximately 80 to 85% of newly diagnosed patients with IDDM, as expected.
The presentation of patients with NIDDM and IDDM in this study were similar. Classic signs and symptoms of diabetes such as polyuria, polydipsia, and polyphagia, are observed in all forms of diabetes and, therefore, unhelpful in discerning the etiology of diabetes. These symptoms and the others assessed including abdominal pain, headache, nocturia, and visual disturbance were shown to be of no clinical or statistical utility in differentiating between IDDM and NIDDM. Only weight loss demonstrated a statistically significant difference between NIDDM and IDDM patients. Weight loss was almost twice as likely to be reported by patients with IDDM. A history of weight loss may be a clinically useful symptom for distinguishing between these two groups, particularly when trying to assess obese youth with diabetes.
Physical characteristics, such as BMI, revealed significant differences between the two groups. NIDDM youths were markedly obese (96% BMI, >85th percentile) but not all patients in the IDDM group were of normal body weight. Twenty-four percent of the IDDM patients had a BMI ≥85th percentile for age. This percentage is consistent with the estimated 21% incidence of obesity in American youths aged 12 to 19 years27 and the estimated 22% for children and adolescents.28 Perhaps as significant as the severity of obesity in the youths with NIDDM was the finding that 86% of the youths were noted at the time of diagnosis to have acanthosis nigricans. Acanthosis nigricans has been linked to hyperinsulinemia and obesity in a randomized screening of schoolchildren29 and Native-American children.30 When insulin concentrations were measured, many of these obese individuals with acanthosis were also found to be hyperinsulinemic. It is interesting that obese patients, regardless of final diagnosis, were 4.6 times more likely to have had some measure of endogenous insulin production than nonobese patients. It is appropriate clinical management that more obese patients had endogenous insulin production assessed. Consequently fewer youths with IDDM had these studies obtained. Because of this collection bias, it is not possible to directly compare the endogenous insulin production between the two study groups.
The occurrence of hyperinsulinism and insulin resistance has been demonstrated to vary among ethnic populations at high risk for NIDDM, including youths of African-American,31Hispanic,32 Pima Indian,33 and Japanese descent.34 Recently, Arslanian and Suprasongsin31 studied a group of healthy adolescents with no family history of diabetes in first degree relatives and found an increase in insulin production and a decrease in insulin sensitivity in African-American participants. It is likely that diminished insulin sensitivity and increased insulin production play a role in the increased incidence of obesity and NIDDM in various ethnic populations. This likely occurs earlier than previously suspected, long before these problems become clinically apparent. It may also explain the childhood/adolescent presentation of obesity and NIDDM in our African-American population.
Another striking finding was the large percentage of NIDDM youths with hypertension at diagnosis. More than one third of these patients were already hypertensive, eight times as frequent as youths with IDDM, probably secondary to their obesity rather than as a complication from their diabetes. Youth-onset hypertension associated with obesity has been demonstrated in several national health surveys.35
The gender and ethnic characteristics of our patient population are very similar to the patients reported from the population-based study conducted in Cincinnati.18 This finding is of particular interest as the study performed in Cincinnati was a large, population-based epidemiologic study designed to determine the incidence of NIDDM in the youths of that area. The population base for this study's referral center is a small urban area and a large rural area. Referral bias cannot be eliminated in this study based on the available data. Despite the differences in the studies population bases, demographics were similar. Female:male ratio between the study populations were almost identical and ethnic representations were similar. African-Americans were overrepresented in the youths with NIDDM from both study populations, whereas IDDM ethnic distribution in Arkansas mirrored the state's ethnic distribution. The youngest patient with NIDDM reported in our study was 8 years old, and 10 years old in the study by Pinas-Hamiel.18 Children as young as 5 years old have been reported among the Pima Indians36 who have the highest reported incidence of NIDDM of any population. They are also considerably more obese than the general population.36 This association between obesity and NIDDM holds true for all ages of Pima Indians presenting with diabetes.36,37
Of the characteristics assessed, history of weight loss, BMI, acanthosis nigricans, and insulin or C-peptide concentration, seem to be the most useful in differentiating between types of diabetes. Interestingly, HbA1C was not useful in distinguishing between types of diabetes as the HbA1C at presentation was the same for both groups. Clearly, the majority of obese youths with diabetes had NIDDM which was supported by the presence of acanthosis nigricans and elevated measures of endogenous insulin production. NIDDM should be considered in the differential diagnosis of youths with new onset diabetes, especially in obese African-American youths with acanthosis nigricans and no history of weight loss. Perhaps with further study a history of no weight loss, which in this study was the only symptom statistically different between the two groups, can be shown to be a reliable predictor of NIDDM. Careful evaluation of these clinical and biochemical characteristics remains important to arrive at the proper diagnosis.
ICA and glutamic acid decarboxylase antibodies, markers of autoimmunity, have been linked to IDDM.38,39 These markers have been detected before onset of clinical diabetes and may remain detectable for years after diagnosis.38 These studies typically take 1 to 2 weeks before results are available, and thus are not useful for immediate decision making at the initial visit. They can confirm the etiology initially suspected, and guide long-term therapy. These markers also have implications for family members of the patient with diabetes.38 Family members of patients with positive ICA and/or glutamic acid decarboxylase antibodies and clinical diabetes are at higher risk for developing IDDM.40 Screening of these family members and preventive therapy is currently under investigation by the National Diabetes Prevention Trial.38,41 Because of the implications for family members, the importance of making the correct diagnosis of a youth with diabetes should not be overlooked.
Initial therapy should be directed by the metabolic derangements at presentation. Patients with DKA require prompt institution of standard DKA therapy, including intravenous insulin, regardless of the suspected diagnosis. If a patient is subsequently found to have evidence of NIDDM, therapy can be tailored appropriately after resolution of DKA, as was seen in the earlier case presentation. Treatment of youths with NIDDM is not well studied and is presently based on experience with adult-onset NIDDM and MODY patients. Oral hypoglycemic agents are effective treatments for both MODY and adult-onset NIDDM.14,42 New therapies directed at blood glucose control in adults may also be effective in youth-onset NIDDM but have not been studied.43-45
Obesity has become a nationwide concern affecting both the adult and pediatric population. Numerous studies have documented the steady increase in adult body weight in this and other countries over the past 30 years.46 National health and nutrition surveys have documented an increase in childhood and adolescent obesity in the United States (US) similar to that seen for adults.9,28,47-51 There was an increase in the prevalence of obesity from 15 to 21% in adolescents 12 to 19 years of age between the years 1980 and 1990.9 Not only are more youths becoming more obese, but the upper centiles of all sexes and races assessed are becoming even more obese.35 In one survey, based on skinfold thickness, the prevalence of obesity in the pediatric population was documented to have increased by 17% and for a subset of this population, the superobese children, 306%.35 Obesity in adults and children has been linked to a number of health concerns, including diabetes.1,3,7-9,35 This association has been established for many ethnic groups, including African-Americans and Native Americans.24,25,52
It is known that the risk of developing NIDDM rises exponentially with increasing body weight in adults.8 This effect was seen even in the nonobese range of women studied in the Nurse's Health Study. From lowest to highest BMI ranges (BMI, 22 to 35 kg/m2) the incidence of NIDDM rose from 13 to 1190 per 100 000 person years.8 Similar findings have been reported in men.7 The mean BMI of the youths with NIDDM reported in this study, 35 ± 1.1 kg/m2, corresponds to the adult group with the highest risk of NIDDM and the most extreme obesity.8 The mean age of these youths with NIDDM was 13.9 years.
Diabetes has become a significant burden on the national health care system. Of the US population, 4.5% had some form of diabetes in 1992 and were responsible for 14.6% (one in seven health-care dollars) of the total US health care expenditure.53 This represents approximately 105 billion dollars annually and does not take into account loss of productivity directly attributable to diabetes. Ninety percent of the estimated 15 million Americans with diabetes have NIDDM (only one half of which have been diagnosed), the remaining 10% have IDDM.12 Each year 160 000 individuals or more die from complications of diabetes making it the sixth leading cause of death in the US.54 Arkansas has recently been ranked as one of 10 states with the highest incidence of obesity in the US.55An estimated 6.8 to 7.5% of the population of Arkansas has some form of diabetes compared with 4.5% for US population.26,53-56It is possible that this increased incidence of diabetes in Arkansas is related to the increased incidence of obesity. These data do not take into account the increase in childhood and adolescent obesity, nor do they include the impact of youth-onset NIDDM.
It seems logical that youths with NIDDM will be at risk for all of the health concerns associated with adult-onset NIDDM such as retinopathy, nephropathy, neuropathy, and macrovascular complications of diabetes. There also are treatment-related complications to be considered, such as hypoglycemia, which can lead to coma, seizures, and even death.57 In addition, because of their extreme obesity, these children are at risk for hypertension, psychological dysfunction, respiratory disease, and several orthopedic conditions.35,49 Childhood and adolescent obesity closely correlate to adult obesity.58 Therefore, these very young patients are likely to have a lifelong battle with not only diabetes but obesity as well. A child developing NIDDM at age 13 years who lives an average lifespan, will have more than 60 years duration of disease.59 Complications of diabetes increase with duration of disease and may develop after only 5 to 10 years of diabetes.60 It is likely that youths with NIDDM will have a major impact on the US health care system as they will have much longer duration of diabetes than their adult counterparts.
Much remains unstudied in these youths. Prospective screening of all youths with diabetes is underway at our facility incorporating all characteristics presented in this paper as well as complete family history, assessment of weight loss, fatigue, measure of endogenous insulin production, markers of autoimmunity, and therapy. Therapy with existing oral hypoglycemic and antihyperglycemic drugs will be assessed. Psychosocial factors and family dynamics affecting the patient/family adherence to therapy and long-term metabolic control are also being assessed.
NIDDM, once believed to be a disease of predominantly obese adults, is on the increase in the pediatric population.18Pinas-Hamiel, et al recently reported that the incidence of adolescent NIDDM in the Greater Cincinnati area increased ten-fold, from .7/100 000 per year in 1982 to 7.2/100 000 per year in 1994.18 This increased incidence in youth-onset NIDDM has corresponded temporally to an unprecedented increase in body weight and prevalence of obesity in the US from 1980 to 1990.9
The increase in the number of youths with NIDDM noted at our facility has continued in 1996 with more than 16 youths diagnosed in the first six months alone. At present, it is unclear if this trend represents a true increase in incidence of NIDDM in our region or reflects increased physician awareness of this problem. All youths presenting with diabetes need a thoughtful evaluation to arrive at the correct diagnosis. Broad assumptions regarding age at presentation should not be the sole diagnostic criteria in the pediatric population to define IDDM, nor should obesity alone be used to diagnose patients with NIDDM. However, lack of weight loss, the presence of obesity, and/or acanthosis nigricans should raise the suspicion that the patient may have NIDDM and may require further evaluation for endogenous insulin production and markers of autoimmunity. It is believed that improved diagnosis will lead to improved medical therapy and better understanding of this challenging medical problem.
- Received September 26, 1996.
- Accepted January 14, 1997.
Reprint requests to (C.R.S.) Arkansas Children's Hospital, Slot 512–6, 800 Marshall St, Little Rock, AR 72202–3591.
Dr Pihoker is now at the Department of Pediatrics, University of Washington, Seattle, WA.
Effective July 1997, Dr Scott will be at the Department of Pediatrics, Medical University of South Carolina, 171 Ashley Ave, 317 Clinical Sciences Bldg, Charleston, SC 29425.
- NIDDM =
- noninsulin-dependent diabetes mellitus •
- MODY =
- maturity onset diabetes of youth •
- BMI =
- body mass index •
- DKA =
- diabetic ketoacidosis •
- CO2 =
- carbon dioxide •
- IDDM =
- insulin-dependent diabetes mellitus •
- ICA =
- islet cell antibodies •
- US =
- United States
- National Diabetes Data Group
- ↵World Health Organization. Report of the Expert Committee on Diabetes. WHO Technical Report Series, No. 646, Geneva, Switzerland: World Health Organization; 1980
- ↵Rewers M, Hamman RF. Risk factors for non-insulin-dependent diabetes. In: Harris MI, ed. Diabetes in America. Washington, DC: US Government Printing Office; 1995:179–220
- ↵Harris MI. Classification, diagnostic criteria, and screening for diabetes. In: Harris MI, ed. Diabetes in America. Washington, DC: US Government Printing Office; 1995:15–35
- Cowie CC,
- Harris MI,
- Eberhardt MS
- Chan JM,
- Rimm EB,
- Colditz GA,
- Stampfer MJ,
- Willett WC
- Sigal RJ,
- Warram JH
- ↵Kenny SJ, Aubert RE, Geiss LS. Prevalence and incidence of non-insulin- dependent diabetes mellitus. In: Harris MI, ed. Diabetes in America. Washington, DC: US Government Printing Office; 1995:37–46
- Fajans SS
- Mohan V,
- Snehalatha C,
- Ramachandran A,
- Viswanathan M
- ↵World Health Organization. Diabetes Mellitus, Report of a Study Group. WHO Technical Report Series, No. 727, Geneva, Switzerland: World Health Organization; 1985
- ↵Frisancho AR. Anthropometric Standards for the Assessment of Growth and Nutritional Status. Ann Arbor, MI: University of Michigan Press; 1993:168
- Umpierrez GE,
- Casals MMC,
- Gebhart SSP,
- Mixon PS,
- Clark WS,
- Phillips LS
- Banerji MA,
- Chaiken RL,
- Huey H,
- et al.
- ↵US Bureau of the Census. United States Population Estimates: 1990 Census Data, Database C90STF3C1, Summary Level: State. Washington, DC: Bureau of the Census; 1993
- Pettitt DJ,
- Moll PP,
- Knowler WC,
- et al.
- Knowler WC,
- Pettitt DJ,
- Savage PJ,
- Bennett PH
- Knowler WC,
- Pettitt DJ,
- Saad MF,
- et al.
- Schatz D,
- Maclaren N
- Tillil H,
- Kobberling J
- Fajans SS,
- Brown MB
- Himms-Hagen J,
- Phil D,
- Danforth E
- Jéquier E
- Kuczmarski RJ
- ↵Cowie CC, Harris MI. Physical and metabolic characteristicss of persons with diabetes. In: Harris MI, ed. Diabetes in America. Washington, DC: US Government Printing Office; 1995:117–164
- ↵Gohdes D. Diabetes in North American Indians and Alaska Natives. In: Harris MI, ed. Diabetes in America. Washington, DC: US Government Printing Office; 1995:683–701
- Pi-Sunyer X
- ↵Centers for Disease Control and Prevention. Health Risks in America. Gaining Insight from the Behavioral Risk Factor Surveillance System. Atlanta, GA: US Department of Health and Human Services, Public Health Service. National Center for Chronic Disease Prevention and Health Promotion; 1995
- ↵Centers for Disease Control and Prevention. Health Risks in America. Behavioral Risk Factor Surveillance System. Atlanta, GA: US Department of Health and Human Services, Public Health Service. National Center for Chronic Disease Prevention and Health Promotion; 1993
- ↵Krolewski AS, Warram JH. Epidemiology of late complications of diabetes. In: Kahn CR, Weir GC, eds. Joslin's Diabetes Mellitus. Philadelphia, PA: Lea & Febiger; 1994:605–619
- Shumei SG,
- Roche AF,
- Chumlea WC,
- Gardner JD,
- Siervogel RM
- ↵US Bureau of the Census. Statistical Abstract of the United States: The National Data Book. Washington, DC: Economics and Statistics Administration; 1995:86
- ↵Wolfsdorf JI, Anderson BJ, Pasquarello C. Treatment of the child with diabetes. In: Kahn CR, Weir GC, eds. Joslin's Diabetes Mellitus. Philadelphia, PA: Lea & Febiger; 1994:530–551
- Copyright © 1997 American Academy of Pediatrics