Presence of anti-DNA antibody in diabetes mellitus: its relation to the duration of diabetes and diabetic complications

In seven patients with insulin-dependent diabetes mellitus (IDDM) and 86 patients with non-insulin-dependent diabetes mellitus (NIDDM), serum anti-DNA antibody was measured by a semiquantitative radioimmunoassay (RIA) method. Prevalence of positive anti-DNA antibody (more than 20 U/mL) was five of seven in IDDM patients, 15 of 36 in NIDDM patients with insulin therapy, and seven of 50 in NIDDM patients without insulin therapy. None of normal subjects or patients with impaired glucose tolerance (IGT) showed positive anti-DNA antibody. The titer of anti-DNA antibody was higher in IDDM patients than in age-matched normal subjects (mean +/- SD; 22.1 +/- 15.3 v 6.5 +/- 2.2 U/mL, P less than .05). In patients with NIDDM, the antibody titer regardless of insulin treatment, was higher than in age-matched subjects with IGT (18.5 +/- 13.1 U/mL in NIDDM patients receiving insulin, 14.8 +/- 8.1 U/mL in NIDDM patients not receiving insulin, and 8.8 +/- 3.9 U/mL in IGT patients [P less than .001] for either of NIDDM groups v IGT). The titer of anti-DNA antibody was positively correlated with the duration of diabetes (r = .413, P less than .001) and with the postprandial blood glucose level (r = .311, P less than .01) in NIDDM patients when all of them were combined and analyzed as a group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired glucose tolerance and diabetes in obesity: a 6-year follow-up study of glucose metabolism

To investigate the time course of glucose metabolism in obesity 33 patients (21 to 69 years old; body mass index [BMI], 25.7 to 53.3 kg/m2) with different degrees of glucose intolerance or diabetes who had been studied initially and 6 years later were submitted to the same 100-g oral glucose tolerance test (OGTT) with indirect calorimetry. From a group of 13 obese subjects with normal glucose tolerance (NGT), four developed impaired glucose tolerance (IGT); from a group of nine patients with IGT, three developed non-insulin-dependent diabetes mellitus (NIDDM); five of six obese NIDDM subjects with high insulin response developed NIDDM with low insulin response. Five patients had diabetes with hypoinsulinemia initially. As previously seen in a cross-sectional study, the 3-hour glucose storage measured by continuous indirect calorimetry remained unaltered in patients with IGT, whereas it decreased in NIDDM patients. A further decrease in glucose storage was observed with the lowering of the insulin response in the previously hyperinsulinemic diabetics. These results confirm cross-sectional studies that suggest successive phases in the evolution of obesity to diabetes: A, NGT; B, IGT (the hyperglycemia normalizing the glucose storage over 3 hours); C, diabetes with increased insulin response, where hyperglycemia does not correct the resistance to glucose storage anymore; and D, diabetes with low insulin response, with a low glucose storage and an elevated fasting and postload glycemia.     

Glucose tolerance behaviour before the onset of type I (insulin-dependent) diabetes in young people as a predictor of the further course of the disease: a retrospective analysis of 33 cases

A study was made of glucose tolerance and insulin secretion in 33 persons who later developed insulin-dependent diabetes (aged 4-24 years) and observation continued further in the first years after manifestation. Patients who developed the typical labile type of diabetes were of normal weight and had either normal glucose tolerance tests before diagnosis or had impaired glucose tolerance (IGT) for a short interval of 2-16 months. Subjects with IGT over a significantly (p less than 0.01) longer period of 32.30 +/- 6.25 (normal body weight) or 94.71 +/- 20.62 (obese) months developed a milder form of diabetes with retarded insulin dependency in obese subjects. The severe and mild form of IDDM are distinct with respect to insulin requirement (0.75 +/- 0.03 or 0.28 +/- 0.04 U/kg b.w., P less than 0.01) and glucagon stimulated C-peptide (0.18 +/- 0.05 or 1.41 +/- 0.27, P less than 0.01) in the first 2.5-3.5 years after onset. The two forms were not different regarding HLA-DR antigens. Islet cell surface antibodies investigated in 15 probands at 27 occasions before diabetes onset had no prognostic value. The development of a mild form of IDDM may be expected in cases with pre-existing IGT for more than one year. The insulin secretion is of low predictive value under these conditions. The observation is of practical use and theoretical interest.     

Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus

Fasting serum total immunoreactive insulin (IRI), true insulin, and true proinsulin (PI) were measured in 169 Pima Indians. The relationship of these variables to glucose tolerance, obesity, and parental diabetes was studied. Seventy-seven subjects had normal glucose tolerance, 46 had impaired glucose tolerance (IGT), and 46 had noninsulin-dependent diabetes mellitus (NIDDM) by WHO criteria. In subjects with normal glucose tolerance, the geometric mean ratio of PI to IRI (PI/IRI) was 10.8% (arithmetic mean, 12.5%), similar to that reported in other ethnic groups with lower prevalence rates of NIDDM. Parental diabetes had no effect on PI/IRI. Obese persons (body mass index, greater than or equal to 27 kg/m2) with normal glucose tolerance had PI/IRI of 9.3% compared with 16.3% for the nonobese (P less than 0.001), and PI/IRI was negatively correlated with body mass index (r = -0.34; P = 0.002). Proinsulin was disproportionately elevated in NIDDM (geometric mean PI/IRI, 19.9%; arithmetic mean, 23.6%), and the degree of elevation was related to the severity of hyperglycemia, but not the duration of diabetes. Subjects with IGT were more obese and had higher fasting plasma glucose (5.7 vs. 5.2 mmol/L; P = 0.025), true insulin (250 vs. 125 pmol/L; P less than 0.001), and PI concentrations (26 vs. 15 pmol/L; P less than 0.001) than those with normal glucose tolerance but similar mean PI/IRI (9.4 vs. 10.8%; P = 0.4). These findings indicate that Pima Indians with NIDDM have a disproportionate elevation of PI consistent with the hypothesis that beta-cell dysfunction associated with hyperglycemia leads to the release of proinsulin-rich immature granules.     

Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes

Summary Nuclear families of non-insulin-dependent diabetic (NIDDM) patients are uncommon, as usually one or both parents have died. In order to aid identification of complete nuclear families, we have ascertained the disease process at a younger age by studying subjects with previous gestational diabetes. One hundred women who had had gestational diabetes, age (±SD) 38 (6) years, were screened by fasting plasma glucose (fpg). Sixty-one were found to have either fasting hyperglycaemia (5.5fpg<7.8 mmol/l) or diabetes. Of these women 35 had both parents alive and the parents of 14 of these women agreed to the assessment of their metabolism by a continuous infusion of glucose with model assessment (CIGMA). Seven probands had impaired glucose tolerance (IGT) and seven were diabetic. They were age 35 (4) years and had body mass index (BMI) 26 (5) kg/m². The parents were aged 62 (6) years and had BMI 29 (6) kg/m² and their affection status was defined as presence of glucose intolerance (fpg or post-infusion achieved plasma glucose level >2 SD of an age and obesity matched population). In the 14 families, five probands (36%) had neither parent affected, six (43%) had one parent affected and three (21%) had both parents affected. Only three probands had a parent with diabetes as defined by World Health Organisation criteria. We concludes that the study of women who have had gestational diabetes allows detection of probands with diabetes or impaired glucose tolerance, who have both parents available for study. A substantial proportion had neither parent affected with impaired glucose tolerance or diabetes, similar to the nuclear families of NIDDM patients. The results are in accord with studies of nuclear families of NIDDM patients in suggesting polygenic inheritance or environmental influences rather than autosomal dominant inheritance with high penetrance.Abbreviations IGT Impaired glucose tolerance - GTT glucose tolerance test - NIDDM non-insulin-dependent diabetes mellitus - fpg fasting plasma glucose - apg achieved plasma glucose - CIGMA continuous infusion of glucose test - BMI body mass index     

Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance

Two hundred and nineteen second generation Japanese-American men were classified with a 75-g oral glucose tolerance test: 77 with normal glucose tolerance, 74 with impaired glucose tolerance (IGT), and 68 with noninsulin-dependent diabetes mellitus (NIDDM). The peak insulin response to the oral glucose load was progressively delayed with each of the 3 glucose tolerance categories. A similar finding was observed with the peak C-peptide response to oral glucose, except for the absence of distinction between IGT and NIDDM. Variables measuring the initial rate of insulin or C-peptide secretion (0-30 min) after oral glucose also demonstrated a progressive diminution with increasing glucose intolerance. The relative incremental insulin response at 30 min and the relative incremental C-peptide response at 30 min were highly correlated with the fasting glucose levels (r = -0.61 and r = -0.62; P less than 0.0001, respectively). Variables measuring the 0-30 min secretory response had high variances, whereas the variance for fasting glucose was low. Twelve men who were initially classified as IGT subsequently developed NIDDM. These 12 men had significantly higher fasting glucose levels at baseline than the remaining men who did not develop diabetes, but the 30 min secretory parameters after oral glucose, although lower in those who subsequently developed diabetes, were not significantly different at baseline. However, if fasting glucose is used as a surrogate measure of secretory response, these 12 men appear to have had an impairment of oral glucose-stimulated insulin secretion antedating the development of NIDDM. The inability of the secretory parameters to detect the abnormality may be due to a type II statistical error, which may be resolved by a larger sample size.     

Plasma islet amyloid polypeptide levels in obesity, impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

We examined the response of plasma islet amyloid polypeptide (IAPP) to an oral glucose load in non-obese and obese subjects with normal glucose tolerance or impaired glucose tolerance (IGT), and in non-obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma IAPP response to intravenous glucagon injection in NIDDM patients was also studied. Plasma IAPP concentration was determined by a sensitive and specific radioimmunoassay. Basal levels of plasma IAPP in non-obese subjects with normal glucose tolerance, IGT and NIDDM were not significantly different from each other. Non-obese subjects with IGT showed delayed and higher plasma IAPP response to oral glucose load compared to normal non-obese subjects. In NIDDM patients, IAPP response to glucose was delayed and lower when compared to normal non-obese subjects. Basal levels of plasma IAPP in normal obese subjects and obese subjects with IGT were significantly higher than those in normal non-obese subjects. Plasma IAPP response to glucose load in these obese subjects was higher than that in normal non-obese subjects. Plasma IAPP response was decreased in diabetic patients treated with diet, oral hypoglycemic agents and insulin in that order. We conclude that the secretion of IAPP is reduced with progression of NIDDM, although it appears to be rather augmented in IGT compared to normal non-obese subjects.     

Effect of differences in glucose tolerance on insulin's ability to regulate carbohydrate and free fatty acid metabolism in obese individuals

The effect of variations in glucose tolerance on insulin's ability to regulate glucose uptake and plasma glucose and FFA concentrations was assessed in 22 obese individuals [8 with normal glucose tolerance, 7 with impaired glucose tolerance (IGT), and 7 with noninsulin-dependent diabetes mellitus (NIDDM)]. Patients with IGT had ambient insulin levels that were higher than normal, associated with elevated postprandial glucose levels and a marked reduction in insulin-stimulated glucose uptake. On the other hand, plasma FFA levels were relatively normal in IGT, possibly because of the hyperinsulinemia. Patients with NIDDM were also hyperinsulinemic, with insulin levels throughout the day that were approximately twice normal. Hyperinsulinemia in patients with NIDDM was associated with a significant decline in insulin-stimulated glucose uptake as well as with significant increases in both ambient plasma glucose and FFA concentrations. Thus, and in contrast to patients with IGT, plasma FFA metabolism in NIDDM was grossly abnormal, despite the concomitant hyperinsulinemia. These data indicate that insulin resistance in obese individuals varies as a function of degree of glucose tolerance, and insulin resistance in patients with NIDDM involves defects in the regulation of both plasma glucose and FFA metabolism.     

High plasma insulin and triglyceride concentrations and blood pressure in offspring of people with impaired glucose tolerance

The plasma glucose and insulin response to an oral glucose challenge, fasting plasma lipid concentration, and blood pressure were compared in 13 offspring of parents previously diagnosed as having impaired glucose tolerance (IGT) and 13 offspring of parents previously shown to have normal glucose tolerance. The parents with IGT had higher plasma glucose, insulin and triglyceride concentration, and blood pressure than parents with normal glucose tolerance. The two groups of offspring were young and non-obese, and similar in terms of age, gender distribution, and body mass index. However, the total integrated plasma insulin response during a 75 g oral glucose tolerance test was significantly higher (p less than 0.05, Student's t-test) in offspring of parents with IGT (718 +/- 71 pmol l-1 h) than in the subjects whose parents had normal glucose tolerance (524 +/- 47 pmol l-1 h). In addition, serum triglyceride concentration was somewhat higher in offspring of parents with IGT (1.17 +/- 0.11 vs 0.92 +/- 0.08 mmol l-1, 0.10 greater than p greater than 0.05), as were both systolic (132 +/- 5 vs 118 +/- 3 mmHg, p less than 0.05) and diastolic (79 +/- 3 vs 70 +/- 2 mmHg, p less than 0.05) blood pressure. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that these changes have a genetic component.     

C-peptide secretion in calcific tropical pancreatic diabetes

Serum C-peptide levels were measured during a glucagon stimulation test in ten normal nonobese controls and 54 diabetic patients with recent onset of diabetes under 30 years of age. Diabetic patients were comprised of 13 CTPD, 23 IDDM, and 18 NIDDM. As similar to IDDM patients, serum C-peptide concentrations did not rise significantly (P greater than 0.05) in response to glucagon administration in CTPD-patients. Mean baseline and peak serum C-peptide concentrations in CTPD-patients were significantly lower (P less than 0.001) than the values in normal controls and NIDDM patients, but were significantly higher (P less than 0.05) than those in IDDM patients. We conclude that CTPD patients have partial C-peptide reserve, which may protect against ketosis and contribute to ketosis resistance in CTPD. Our results also suggest that CTPD patients require insulin treatment. Neither baseline nor peak C-peptide levels after glucagon could discriminate CTPD from IDDM and CTPD from NIDDM.     

Prevalence of non-insulin-dependent diabetes mellitus in Asian Indian families with a single diabetic parent

Offspring of one parent diabetic (OPDR-A) and offspring of one parent diabetic with a first-degree family history on the non-diabetic parental side (OPDR-B) were studied to assess the influence of familial aggregation on the prevalence of non-insulin-dependent diabetes mellitus (NIDDM). All parents and offspring were tested for diabetes by oral glucose tolerance test. All parents had NIDDM. The prevalence of diabetes was 36% and 54% in the OPDR-A and OPDR-B families, respectively. The prevalence rate in OPDR-B was higher compared to OPDR-A families (P less than 0.01). The prevalence of diabetes in OPDR families was not different whether the father or the mother had diabetes. There was a male predominance among the diabetic offspring. The age at diagnosis was lower in the offspring compared to that in their parents in both groups. The expected risk of diabetes was greater in OPDR-B families compared to OPDR-A families. Thus it is seen that there is high prevalence of NIDDM in our population even in families with only one diabetic parent.     

The Clinical Implications of Impaired Glucose Tolerance

Impaired glucose tolerance (IGT) was introduced in 1979 as an intermediate category covering the grey area between unequivocal diabetes mellitus and risk free more normal glucose tolerance. The IGT group included those at high risk of subsequent development of non-insulin-dependent diabetes mellitus (NIDDM) but low risk of specific diabetic complications. Categorisation of subjects as IGT is hampered by the variability of the oral glucose tolerance test, but even those shown to be IGT only once are at increased risk of developing NIDDM. The relative roles of inheritance, fetal undernutrition, and environmental life style factors (physical inactivity and diet) in the aetiology and pathogenesis of IGT are discussed, with all contributing. The prevalence of IGT in different populations has now been widely studied with values ranging from 2 to 25% in adults. Rates of progression to NIDDM also vary widely from 2 to 14% per year. Risk factors for progression are discussed. IGT also carries an increased risk of development of cardiovascular disease (CVD) and forms part of the “metabolic syndrome”. The role of insulin resistance as a common aetiological factor is briefly reviewed. Finally, possible means of treatment of IGT are listed with the intent of delaying the onset of diabetes and CVD, which is of obvious clinical importance.     

Mortality of Japanese diabetics in a seven-year follow-up study

To clarify the prognosis of Japanese diabetics, 143 patients with IDDM, 3394 with NIDDM and 384 with IGT who had visited the Diabetes Center of the Tokyo Women's Medical College from 1976 through 1980 were followed up during 3-7 years. The follow-up rates of the patients with IDDM, NIDDM and IGT were 100.0%, 99.6% and 99.7%, respectively. The mortality rates per 1000 person-years among the patients with IDDM, NIDDM and IGT were 8.73%, 25.24 and 13.72, respectively. On the other hand, the ratios of observed number of deaths among diabetics to expected number of deaths among a sex- and age-matched general population were 3.39 in IDDM, 1.55 in NIDDM and 1.03 in IGT. The leading cause of death in IDDM was acute cardiac failure and in both NIDDM and IGT, malignant neoplasms. In NIDDM, a statistically significant excess of deaths from diabetes mellitus itself, ischemic heart disease and malignant neoplasms was observed compared with the general population. This is the first report concerning mortality and causes of death among Japanese diabetics separately for IDDM, NIDDM and IGT.     

Non-linkage of the glucagon-like peptide 1 receptor gene with maturity onset diabetes of the young

Summary Glucagon-like peptide-1 (GLP-1) is a hormone derived from the preproglucagon molecule that is secreted by intestinal L cells and stimulates insulin secretion from betacells. The GLP-1 receptor is a candidate gene for diabetes mellitus, as mutations may induce the impaired insulin response that is a characteristic feature of NIDDM. To study the relationship between the GLP-1 receptor gene and NIDDM, linkage of a microsatellite polymorphism flanking the GLP-1 receptor gene with diabetes was investigated in three Caucasian families with MODY and in the nuclear families of 12 NIDDM probands. A cumulative LOD score –8.50 excludes linkage in these MODY pedigrees. A LOD score of –1.24 in the NIDDM nuclear pedigrees makes linkage improbable. Mutations in or near the GLP-1 receptor gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but we cannot exclude a role for this locus in a polygenic model or a major role in some pedigrees.Abbreviations GLP-1 Glucagon-like peptide-1 - NIDDM noninsulin-dependent diabetes mellitus - MODY maturity onset diabetes of the young - LOD logarithm of the odds for linkage vs non-linkage - IGT impaired glucose tolerance - bp base pair     

Fatty acid composition of serum cholesterol esters in different degrees of glucose intolerance: a population-based study

The fatty acid composition of serum cholesterol esters was investigated in 325 subjects with normal glucose tolerance, 97 subjects with impaired glucose tolerance (IGT), and 98 subjects with non-insulin-dependent diabetes mellitus (NIDDM) identified by population-based screening. The proportions of palmitic acid (16:0) and palmitoleic acid (16:1) in serum cholesterol esters increased from the normal glucose tolerance group to the IGT and diabetic groups. On the other hand, the proportion of linoleic acid (18:2) was lower in diabetic subjects than in the subjects with IGT or normal glucose tolerance. The proportions of gamma-linolenic (18:3), dihomo-gamma-linoleic (20:3), and arachidonic (20:4) acids were highest in diabetic subjects and lowest in subjects with normal glucose tolerance. Our findings suggest that subjects with NIDDM or IGT have had higher dietary intake of saturated fatty acids. Both serum insulin and blood glucose concentrations probably have an effect on the elongation and desaturation of fatty acids, but the metabolism of linoleic acid to prostaglandin precursors seems to be different in different types of diabetes, NIDDM patients showing no abnormalities. The possibility that the fatty acid composition of plasma and membrane lipids has a role in insulin resistance and blood glucose regulation deserves further investigation.     

Can insulin resistance exist as a primary defect in noninsulin-dependent diabetes mellitus?

In this study we have attempted to quantify the plasma insulin response to glucose and insulin action in 22 nonobese subjects: 11 with normal glucose tolerance and 11 with mild [mean fasting plasma glucose concentration, 128 +/- (+/- SEM) 5 mg/dL] noninsulin-dependent diabetes mellitus (NIDDM). Estimates of the plasma insulin response were made by determining the plasma insulin concentration at hourly intervals from 0800-1600 h, before and after mixed meals consumed at 0800 h (breakfast) and 1200 h (lunch). Insulin action was assessed by measuring glucose uptake during insulin clamp studies performed at steady state plasma insulin levels of approximately 10 and 60 microU/mL, with the difference between the 2 values defined as insulin-stimulated glucose uptake. Plasma glucose (P less than 0.001) and insulin (P less than 0.001) concentrations were significantly higher in patients with NIDDM throughout the 8-h period (by two-way analysis of variance). However, mean (+/- SEM) insulin-stimulated glucose uptake was markedly reduced (P less than 0.001) in patients with type 2 diabetes mellitus (112 +/- 72 vs. 336 +/- 44 mg/m2 min-1). Thus, patients with NIDDM and mild fasting hyperglycemia were both insulin resistant and hyperinsulinemic compared to normal individuals. These data indicate that a defect in insulin-stimulated glucose uptake can occur in NIDDM in the absence of significant hyperglycemia and/or hypoinsulinemia.     

Urinary C-peptide as an index of unstable glycemic control in insulin-dependent diabetes mellitus (IDDM)

In order to investigate whether urinary C-peptide (UCP) excretion can be a useful index of insulin-dependent diabetes mellitus (IDDM) with unstable glycemic control, UCP was measured in nine IDDM patients with unstable glycemic control, nine IDDM patients with stable glycemic control, and 12 non-insulin-dependent diabetic (NIDDM) patients treated with insulin. The UCPs in overnight urine (U1) and fasting single void urine (U2) in IDDM patients with unstable glycemic control were significantly lower than those in IDDM patients with stable glycemic control (U1: 0.03 +/- 0.03 vs 0.24 +/- 0.20 nmol/mmol-Creatinine, U2: 0.02 +/- 0.01 vs 0.20 +/- 0.20 nmol/mmol-Cr, mean +/- SD, both P less than 0.01). The UCPs in U1 and U2 in both groups of IDDM were significantly lower than those in NIDDM (U1: 0.97 +/- 0.52, U2: 0.73 +/- 0.41 nmol/mmol-Cr, both P less than 0.01). The UCPs in U1 and U2 significantly correlated with incremental C-peptide response to intravenous glucagon injection and with glycemic stability assessed by the standard deviation of 10 previous fasting plasma glucose levels. These results suggest that UCP reflects their residual insulin secretory capacity and that UCP can be a useful index which distinguishes patients with unstable IDDM from those with stable diabetes mellitus.     

Poor physical fitness,and impaired early insulin response but late hyperinsulinaemia,as predictors of NIDDM in middle-aged Swedish men

Summary In a prospective population-based study of middle-aged Caucasian men, performed in Malmö, Sweden, specifically designed to evaluate physical fitness, early and late insulin response as predictors of non-insulin-dependent diabetes mellitus (NIDDM), 4,637 non-diabetic men underwent oral glucose tolerance tests at the ages of 48 and 54 years. At the baseline examination, physical fitness was measured in terms of lung vital capacity and oxygen uptake during ergometry; early insulin response in terms of the 40-min insulin increment during an oral glucose tolerance test (a correlate of acute insulin response to an intravenous glucose tolerance test), and late insulin response were measured in terms of the 2-h insulin value during the oral glucose tolerance test (a correlate of glucose disposal during euglycaemic clamp testing). Of the subjects studied 116 developed NIDDM (0.4% annually), and when compared with non-diabetic men at baseline, they were found to have an 11% higher mean body mass index (p<0.001), a higher frequency of family history of diabetes (31 vs 18%, p<0.001), 16% lower mean physical activity index (p<0.05), 16% lower mean estimated maximal oxygen uptake (p<0.001), 10% lower mean vital capacity (p<0.001), 26% lower 40-min to total insulin response ratio (p<0.001), and a 2.7 times higher mean 2-h insulin value during an oral glucose tolerance test (p<0.001). Regression analysis (using Cox's proportional hazards model) showed both low vital capacity, and impaired early insulin response but late hyperinsulinaemia to be independent predictors of NIDDM, in addition to body mass index and fasting blood glucose level (p=0.05–0.0001). Among subjects with impaired glucose tolerance at baseline (44 of 278 developed NIDDM), fasting glucose level alone predicted diabetes in this model. The findings suggest that in this age group in a Caucasian population, not only does insulin resistance precede glucose intolerance and NIDDM, but also loss of early insulin response indicating impaired beta-cell function to be an early feature of the process culminating in diabetes. As both physical fitness [which correlates inversely with late insulin response (r=–0.42, p<0.0001)], and the level of physical activity were shown to correlate with diabetes development in this large series, measures to correct these adverse features should be included in future strategies for preventing NIDDM.Abbreviations OGTT Oral glucose tolerance test - NGT normal glucose tolerance - IGT impaired glucose tolerance - NIDDM non-insulin-dependent diabetes mellitus - BMI body mass index - IVGTT intravenous glucose tolerance test     

Exocrine Pancreatic Ductograms in Insulin-dependent Diabetes Mellitus

Objectives: To examine the prevalence of abnormal pancreatic ductograms in patients with insulin-dependent diabetes mellitus (IDDM) and to determine the clinical cbaracteristics of those patients. Methods: Panereatie exocrine morphology was studied by endoscopie retrograde pancreatography (ERP) in 43 patients with IDDM, 12 patients with islet cell antibody (ICA)-positive non-insulin-dependent diabetes mellitus (NIDDM), and 22 patients with ICA-negative NIDDM. Resuits: ERP revealed a significantly higher prevalence of abnormal pancreatic ducts (dilation and stenosis, tortnosity, obstruction, and intraductal calculi) in the patients with IDDM (17/43, 40%) than in the patients with ICA-negative NIDDM (2/22, 9%, p = 0.018). IDDM patients who slowly progressed to insulin dependency more than 13 months after the onset of diabetes had a higher frequency of abnormal pancreatic ducts (13/22, 59%) than those who needed insulin therapy within 12 months after the onset (4/21, 19%, p = 0.016). There was no difference in duration of diabetes between the two groups. ICA-positive NIDDM patients also had a higher frequency of abnormal pancreatic ducts (7/12, 58%) than ICA-negative NIDDM patients (2/22, 9%, p = 0.0074). Conclusions: These results indieate that a high proportion of IDDM patients who have prolonged histories of non-insulin dependency with ICA suffer pancreatic exocrine impairment. A similarity between IDDM with a slowly progressive clinical course and fibrocalculous pancreatic diabetes seen in tropical countries also was suggested.     

Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome

Racial origin and family history of type 2 diabetes impact upon the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes, both of which are common in women with polycystic ovary syndrome (PCOS). We examined the effects of race and family history of type 2 diabetes on the risk of IGT and type 2 diabetes in a large cohort of women with PCOS. Data obtained at baseline were analyzed from 408 premenopausal women with PCOS. Multivariate linear regression models were used to assess the impact of race (white, black, and other) and family history of type 2 diabetes on body mass index, waist circumference, and waist to hip ratio; glycemic measures (glucose and insulin levels obtained during a standard 75-g oral glucose tolerance test, fasting glucose to insulin ratio, and homeostasis model assessment model of insulin resistance derived from fasting levels of glucose and insulin), hemoglobin A(1c), and SHBG, and dehydroepiandrosterone sulfate levels. Sixteen (4%) of the 408 patients had type 2 diabetes, 94 (23%) had IGT, and the remaining 298 (73%) had normal glucose tolerance. A history of type 2 diabetes in either parent (FHxPOS) was present in seven (44%) of the 16 diabetic women with PCOS, 37 (39%) of the 94 women with IGT, and 62 (21%) of those with normal glucose tolerance (P < 0.01, by chi(2) test). The prevalences of IGT and type 2 diabetes were significantly higher in FHxPOS PCOS women compared with FHxNEG PCOS women, IGT evident in 37 (35%) FHxPOS compared with 57 (19%) FHxNEG women, and type 2 diabetes evident in seven (7%) FHxPOS compared with nine (3%) FHxNEG women. Among the 392 nondiabetic subjects, after adjustment for the effects of race, FHxPOS differed significantly from FHxNEG patients in having a higher mean waist to hip ratio, hemoglobin A(1c) level, 2-h glucose level, fasting glucose and insulin levels, glucose to insulin ratio, homeostasis model assessment model of insulin resistance, and areas under the glucose and insulin curves during the oral glucose tolerance test. A family history of type 2 diabetes was present with a significantly greater frequency among women with PCOS who had IGT or type 2 diabetes compared with those with normal glucose tolerance. Conversely, a family history of type 2 diabetes in a first-degree relative was associated with a significantly higher risk for IGT or type 2 diabetes in women with PCOS. Even among nondiabetic women with PCOS, a positive family history of type 2 diabetes was strongly associated with metabolic characteristics associated with an increased risk for type 2 diabetes. Finally, the fasting glucose concentration was poorly associated with 2-h glucose concentrations among PCOS women with IGT, suggesting that the fasting glucose concentration is inadequate to predict the presence of IGT in PCOS.