Glucose tolerance and insulin response in parents of patients with insulin-dependent and juvenile-onset non-insulin-dependent diabetes mellitus.

Glucose tolerance and insulin response were examined using a 100 g oral glucose tolerance test (OGTT) in 108 parents of 23 patients with insulin-dependent (IDDM) and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose age of onset of diabetes was less than 35 years. Thirty-two age-matched healthy volunteers without a family history of diabetes were also examined as a control group. Diabetes and impaired glucose tolerance (IGT) were significantly more frequent in parents of NIDDM (diabetes 34%, IGT 27%) than in parents of IDDM (diabetes 7%, IGT 13%) (P less than 0.001). At least one parent had diabetes or IGT in 30% of IDDM and 84% of NIDDM patients (P less than 0.001), and both parents had diabetes or IGT in 9% of IDDM and 39% of NIDDM patients (P less than 0.02). Even in cases with 'normal' glucose tolerance, the mean plasma glucose was higher in parents of NIDDM than in control subjects, suggesting a high prevalence of abnormal glucose tolerance including the marginal degree of abnormality in the families of NIDDM. The early phase insulin response was decreased more among parents of NIDDM with the greater impairment of glucose tolerance. However, among those with 'normal' glucose tolerance, early phase insulin response did not differ between parents of IDDM and NIDDM, and control subjects. The results confirmed a stronger familial background in NIDDM patients of younger onset than in IDDM. The different patterns of glucose tolerance among two parents of young-onset NIDDM patients suggest heterogeneity of the mode of inheritance of NIDDM among families.     

Immunogenetic and nutritional profile in insulin-using youth-onset diabetics in Korea.

There are few reports on the genetic, immunological and nutritional characteristics of insulin-using youth-onset diabetes mellitus, insulin-dependent diabetes mellitus (IDDM) and malnutrition-related diabetes mellitus (MRDM) in Korea. Among 1266 hospitalized Korean diabetics, 29 (2.3%) were IDDM and 84 (6.6%) were MRDM. A diabetes history of first-relatives (28.6%) was more frequently found in the MRDM group than in the IDDM (14.8) and non-insulin-dependent diabetes mellitus (NIDDM) (19.0%) groups. HLA-DR4 was more common among IDDM (54.2%) and MRDM (52.4%) patients than controls (26.3%), and HLA-DR3 was more common among only IDDM patients (29.2%) than controls (10.9%). Conventional islet-cell antibodies were detected in 8 of 15 IDDM patients tested (53.3%) and in 11 of 22 MRDM patients (50.0%). MRDM patients had higher serum basal (1.02 +/- 0.51 ng/ml) and peak (1.44 +/- 0.76 ng/ml) C-peptide concentrations than IDDM patients, but lower concentrations than NIDDM patients. Before the onset of diabetes, the calorie intake of 21 MRDM patients assessed was 63.1% of the daily requirement and the intake of carbohydrate, protein and fat was 71.7%, 55.9% and 39.8%, respectively. In summary, our data suggest that IDDM in Korea is associated with HLA-DR3 or HLA-DR4, indicating a risk for IDDM in Western societies; furthermore, MRDM has a history of undernutrition at the preonset period and is also associated with HLA-DR4. It might be also concluded that MRDM in Korea is another expression of IDDM caused by the shortage of some nutrients for the structural and/or functional maintenance of pancreatic beta-cells.     

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.     

The frequency and severity of retinopathy are related to HbA1c values after, but not at, the diagnosis of NIDDM

OBJECTIVES: To examine the relationship between previous glycaemic exposure and prevalence of retinopathy 8 years after diagnosis of diabetes in 58 islet cell antibodies (ICA)-negative noninsulin-dependent diabetes mellitus (NIDDM) patients and in a group of 14 ICA-positive 'NIDDM' and insulin-dependent diabetes mellitus (IDDM) patients. DESIGN AND METHODS: The Wisconsin retinopathy scale was used to assess the retinopathy which was graded into mild, moderate and severe nonproliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR). The frequency and severity of retinopathy was related to HbA1c levels at diagnosis, and 3 and 5 years later. RESULTS: Thirty of the 58 ICA-negative NIDDM patients (52%) but only 2 of the 14 ICA-positive 'NIDDM' or IDDM patients (14%) had mild-moderate-severe NPDR 8 years after diagnosis (P = 0.02). None had PDR. Retinopathy 8 years after diagnosis in NIDDM (= 58 ICA-negative patients) was correlated with the degree of glycaemic control (HbA1c levels) at 3 and 5 years after diagnosis, but not to HbA1c levels at diagnosis. The relative risk for a higher average HbA1c (per percentage) at 3 and 5 years was 1.56 for any retinopathy vs. no retinopathy (95% confidence interval 1.1-2.2; P = 0.01) and 1.68 for moderate to severe NPDR in comparison with no DR and mild NPDR (95% confidence interval 1.0-2.8; P = 0.04). CONCLUSIONS: Retinopathy after 8 years of diabetes in NIDDM patients was associated with impaired glycaemic control during previous years but not with glycaemic control at baseline. Good glycaemic control may prevent retinopathy in patients with NIDDM.     

Anti-GAD antibodies in Chinese patients with youth and adult-onset IDDM and NIDDM

Summary An autoimmune basis for the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is supported by the frequent presence of autoantibodies – islet cell antibodies (ICAs) and GAD antibodies (GADab). However, in Chinese patients with clinical IDDM, a low prevalence of ICAs was observed. In non-insulin-dependent diabetic (NIDDM) patients, it has been suggested that the presence of GADab may identify a subset of latent autoimmune diabetes in adults (LADA). We determined the frequency of GADab in a large group of 134 IDDM and 168 NIDDM Chinese patients, and assessed the relation with ICAs status. Results showed that 39.6 % IDDM and 16.1 % NIDDM patients had GADab, and 20.1 % and 4.8 %, respectively had detectable ICAs. Frequency of GADab positivity was not influenced by whether the patients had youth or adult-onset IDDM or NIDDM, or by duration of diabetes. NIDDM patients seropositive for GADab shared similar clinical characteristics and fasting C-peptide levels with those who were GADab negative. Presence of GADab therefore did not serve to identify a sub-group of patients with latent or slow-onset IDDM. Half (53 %) of our IDDM patients had neither GADab nor ICAs. The reason for this observation is unclear. One theory is that other autoantigens yet to be identified may be contributory. Alternatively, in the Chinese, autoimmunity may not be the major factor in the pathogenesis of IDDM. [Diabetologia (1997) 40: 1425–1430] Received: 11 March 1997 and in revised form: 13 May 1997     

Glycated Haemoglobin Levels in Patients with Diabetes in One General Practice over a 10-year Period

The aim of the study was to evaluate the level of control, as reflected by HbA_1c, in patients with diabetes attending one general practice over a 10-year period. The study was based in one general practice in South Tyneside, UK and consisted of an analysis of HbA_1c values of all patients with diabetes attending the practice between 1983 and 1992. HbA_1c levels were analysed and are presented as multiples of the standard deviation above the mean. In the practice 256 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 76 with insulin-dependent diabetes mellitus (IDDM), attended for a total of 1596 doctor/patient contacts in the diabetic clinic over 10 years. The prevalence of diabetes was 1.9%. Over the course of the clinic, in any one year, 25% of patients with NIDDM and 55% with IDDM had levels of HbA_1c above those thought to be associated with increased risk of microvascular complications. Significant reduction in glycated haemoglobin (HbA_1c) occurred in the first year after diagnosis (p < 0.01) and after changing treatment from diet alone to diet and oral hypoglycaemic agents (p < 0.001). We conclude that a large proportion of patients within this population had levels of glycaemic control that put them ‘at increased risk’.     

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.     

Age of onset and type of Japanese younger diabetics in Tokyo

The age of onset of diabetes and the type of diabetes were examined in 1408 Japanese patients who were initially diagnosed as having diabetes under the age of 30 and were registered in our Diabetes Center between 1980 and 1989. Of the 1408 patients, 538 (38.2%) had insulin-dependent diabetes mellitus (IDDM) (male/female ratio of 2:3), and 870 (61.8%) had non-insulin-dependent diabetes mellitus (NIDDM) (male/female ratio of 5:4). There were significant differences of the sex ratio in both IDDM and NIDDM. The age at which the numbers in both the IDDM and NIDDM groups were almost equal was 13–14 (26 for IDDM and 23 for NIDDM at 13; 28 for IDDM and 30 for NIDDM at 14). A total of 58% of IDDM patients (22% of all patients) and only 6% of NIDDM patients (4% of all patients) were diagnosed under the age of 14 (P < 0.01). Of the patients with IDDM, 42% (16% of all patients) were diagnosed over the age of 14, as were 94% of NIDDM (58% of all patients). The percentage of NIDDM cases increased even more over the age of 28, and no NIDDM patients developed diabetes under the age of 9.     

Analysis of diabetic family connection in subjects with insulin-dependent diabetes mellitus (IDDM)

The family connection of diabetes was examined from the clinical records of 3,372 subjects who were seen, as an out patient population, within the frame of a Regional Health Program in Taranto, South Italy. The family connection of diabetes resulted from a questionnaire in which the subjects had to give informations about their disease, if present, and degrees of relationship that were directly verified by us with the examination (clinic and laboratory) of relatives said to have diabetes. From the analysis of records, it emerged that 112 patients were affected by insulin-dependent-diabetes mellitus (IDDM): 54 of them were related with at least one subject suffering from noninsulin-dependent diabetes mellitus (NIDDM), 13 with at least one subject affected by IDDM and the remaining 45 did not show any family connection. The corresponding figures found in a group of healthy control subjects, matched to IDDM patients for age, sex and BMI, were 19, 2 and 84, respectively (p less than 0.001). 34 IDDM patients were related with a first degree of relationship (parents, sons, sibs) to diabetic subjects (IDDM or NIDDM), but only 4 controls showed such a degree (p less than 0.001). These results seem to indicate that patients with IDDM have an increased family history of NIDDM.     

Phosphodiesterase activity in human subcutaneous adipose tissue in insulin- and noninsulin-dependent diabetes mellitus

The influence of diabetes mellitus on phosphodiesterase (PDE) activity in human sc adipose tissue was investigated in 8 patients with insulin-dependent (IDDM) and 9 with noninsulin-dependent (NIDDM) diabetes mellitus. The results were compared with data from 10 healthy normal weight subjects. The apparent maximal PDE activity (Vmax) of the low Km form of PDE was 60% lower (P less than 0.01) in untreated IDDM and NIDDM than in the control state. After treatment of IDDM and NIDDM, the Vmax of the low Km PDE was normalized. In untreated IDDM and NIDDM, the Vmax of the low Km PDE was correlated to the cAMP level (r = 0.8). This correlation was not observed after antidiabetic treatment or in the control state. The apparent Vmax values of the high Km form of PDE were similar in the diabetic states and in control subjects. The results suggest that the low Km PDE is inhibited in untreated IDDM and NIDDM. In these conditions, PDE may be one factor responsible for regulation of the cAMP level.     

Non-insulin-dependent diabetes and renal replacement therapy

Reports of renal replacement therapy in diabetes usually refer to patients with insulin-dependent diabetes mellitus (IDDM) only, and little is known about renal failure in non-insulin-dependent diabetics (NIDDM). A high proportion, 46/141 (32%), of the diabetics treated at our unit since 1974 had NIDDM. They were older at treatment (56 +/- 9 years, mean +/- SD) compared to the IDDM patients (39 +/- 10 years, p less than 0.001), and had a shorter duration of diabetes (13 +/- 8 years versus 23 +/- 8 years, p less than 0.001). Asians and Afro-Caribbeans accounted for 48% of the NIDDM patients (22/46) compared to only 7% of those having IDDM (6/95, p less than 0.0001). Non-diabetic renal disease accounted for the renal failure in 32% (15/46) of the NIDDM patients but only in 10.5% (10/95) of the IDDMs (p less than 0.001). Despite these differences the prevalence of other diabetic complications (retinopathy, neuropathy, and cardiovascular disease) was similar. Patient survival after transplantation was poorer in NIDDM than IDDM (23% and 57%, respectively, at 2 years). Survival on dialysis was equally poor in NIDDM and IDDM. Thus, NIDDM patients treated for renal failure are more commonly non-European and more often have non-diabetic renal disease. Yet other diabetic complications occur to the same extent in both IDDM and NIDDM patients with diabetic nephropathy.     

Left ventricular systolic function in middle-aged patients with diabetes mellitus

In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control Subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow-up was 1.1 ± 1.1% (mean ± SEM) in control subjects, 3.1 ± 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 ± 1.4% (p <0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (<50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p <0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by <5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination. In patients with IDDM, the respective increase was from 43% to 52% (p = NS, compared With control subjects), and in patients with NIDDM from 53% to 73% (p = NS). Duration and metabolic control of diabetes, presence of diabetic complications, and LVEF at rest or during exercise at baseline did not differ in either diabetic group between the patients who had normal or abnormal LVEF at rest or in response to exercise at follow-up examination. No study subject experienced clinical heart failure during follow-up, but 7% of control subjects, 37% of patients (p <0.001) with IDDM, and 34% of patients (p <0.01) with NIDDM had coronary artery disease at follow-up examination. In conclusion, LVEF at rest deteriorated significantly during 4-year follow-up in patients with NIDDM but not in patients with IDDM. A high prevalence of subclinical LV systolic dysfunction became evident both in patients with IDDM and patients with NIDDM as an abnormal LVEF response to exercise both at baseline and follow-up examinations.     

Celiac disease and insulin-dependent diabetes mellitus

We screened for celiac disease, by means of IgA class anti-endomysium antibodies (EmA), 383 consecutive adults with insulin-dependent diabetes mellitus (IDDM). Two control populations entered the study as well: 151 adults with biopsy proven celiac disease, as true positives; and 520 controls (healthy and diseased) as true negatives. IgA-EmA positivity was found in 145 of 151 (96%) celiac disease patients but in none of the controls (100% specificity). EmA were positive in 12 of 383 (3.13%) IDDM patients: 10 of these positives underwent intestinal biopsy, which showed either partial or total villous atrophy. Only one patient presented with gastrointestinal complaints, but severe iron deficiency was found in all. The IDDM celiac patients were started on a gluten-free diet: four refused both the diet and the follow-up protocol. Approximately one year after gluten withdrawal no significant change in the degree of diabetes control was observed, while an increased requirement for insulin was observed in three of four patients who strictly complied with the diet. The prevalence of biopsy-proven celiac disease among adult IDDM patients (1:38), eight times higher than that recently estimated for the general Italian population and the absence, except in one case, of gastrointestinal symptoms emphasizes the benefit of screening programs on populations at risk.     

Islet cell surface antibodies by an ELISA method in diabetic and nondiabetic patients

Islet cell surface antibodies (ICSA) were investigated by an ELISA method using a commercial kit in 146 subjects with and without islet cell antibodies (ICA): 28 with insulin-dependent diabetes mellitus (IDDM), 24 with noninsulin-dependent diabetes mellitus (NIDDM), 22 first-degree relatives (FDR) of IDDM patients, 31 organ-specific autoimmune patients (OSAP), 21 nonautoimmune hospitalized patients (NAP), and 20 ICA-negative normal controls. Furthermore, insulin autoantibodies (IAA) were evaluated in 87 of these subjects. ICSA were found in 11% of IDDM patients and in 14% of their FDR, in 4% of NIDDM patients, in 10% of OSAP, in 10% of NAP, and in 5% of normal controls. After absorption with rat liver powder, ICSA were detected in 7% of IDDM patients, in 5% of their FDR, in 4% of NIDDM, in 6% of OSAP, in 5% of NAP and in none of normal controls. ICSA were also detected in 4% of IAA-positive compared to 3% of IAA-negative sera. Neither correlation was found between ICSA and ICA in each group of subjects, nor between ICSA and IAA, suggesting that these autoantibodies recognize different pancreatic targets. Moreover, no significant difference was observed for ICSA prevalence in the various groups of patients studied when compared with normal controls. The prevalence of ICSA assessed by this ELISA method has been compared to that reported by other workers, who employed different techniques.(ABSTRACT TRUNCATED AT 250 WORDS)     

High frequency of autonomic as well as peripheral neuropathy in patients with malnutrition-related diabetes mellitus

We assessed peripheral and autonomic nerve function in 27 diabetics. Ten had malnutrition-related diabetes mellitus (MRDM), eight insulin-dependent diabetes mellitus (IDDM), and nine non-insulin-dependent diabetes mellitus (NIDDM). The frequency of peripheral neuropathy was 70, 78 and 13% in MRDM, NIDDM and IDDM respectively. Furthermore, the frequency of abnormality in cardiac beat-to-beat variation was 50 and 38% in MRDM and IDDM respectively, whereas our NIDDM patients did not show this abnormality. The patients with MRDM thus revealed a high frequency of not only peripheral but also autonomic neuropathy. Autonomic dysfunction appears to be a new characteristic of MRDM, not mentioned by the WHO study group.     

Epidemiology of childhood diabetes in Osaka District, Japan, using the documents from the medical benefits system specific for childhood diabetes.

For an epidemiological study of childhood diabetes, application forms for medical benefits filed in Osaka Prefecture were collected and analyzed. A total of 465 patients with childhood diabetes under 18 yr of age were identified during the period between 1978 and 1988; 371 (175 boys and 196 girls) of them were classified as insulin-dependent diabetes mellitus (IDDM), and the others were either non-insulin-dependent diabetes mellitus (NIDDM) or an unidentified type of diabetes. The mean annual incidence of IDDM was 1.68 for boys and 2.00 for girls per 100,000 population, the rate being slightly higher for girls. The rates increased among older children, with a peak in the 10-14-yr age group. The prevalence estimated on the basis of the cumulative incidence in 1988 was 1.29 for boys and 1.60 for girls per 10,000 population, indicating a marked increasing trend with age. A significant seasonal variation was observed in the months of onset for IDDM, with higher rates during the winter. The mean birth weights of the male and female patients with IDDM were slightly lower than the national means. Use of official documents obtained from the medical benefits system was found to be an effective method for identification of cases of IDDM in the community, although further information is required for more accurate confirmation of such cases.     

The Gulf War and Diabetes Mellitus

The Gulf war was a traumatic and stressful event for the inhabitants of Tel-Aviv and vicinity. The entire population changed its way-of-life. In order to evaluate the influence of the war stress on glucose control, we reviewed the charts of all diabetic patients attending the outpatient clinics at the Tel-Aviv Medical Centre, whose weight and glycated haemoglobin was determined between 15.1.91 and 2.5.91 (the war period), with comparative measurements within 4 ½ months both before and after these dates. Sixty-six patients with non-insulin dependent diabetes mellitus (NIDDM) and 16 with insulin-dependent diabetes mellitus (IDDM) were examined. During the war, their glycated haemoglobin increased by 10.1 to 10.9% and from 9.6 to 10.2%, respectively. Weight increased from 76.1 to 77.5 kg in the NIDDM and from 63.2 to 64.7 kg in the IDDM patients. Both measurements returned to baseline after the war. No correlation was found between the changes in glycated haemoglobin and weight.     

Anthropometric studies in diabetes in the Tropics

Summary Anthropometric studies were carried out in three groups of diabetics seen in southern India, namely fibrocalculous pancreatic diabetes (FCPD) (n=49) (a subtype of malnutrition related diabetes), insulin dependent diabetes mellitus (IDDM) (n=55) and non-insulin dependent diabetes mellitus (NIDDM) (n=104). Both FCPD and IDDM had significantly lower body mass index, skinfold thickness (triceps, biceps, subscapular and suprailiac), mid-arm circumference and fat mass compared to controls and NIDDM patients, (p<0.001 for all parameters). FCPD and IDDM males did not show any significant differences in any of the anthropometric parameters studied. Among the females, FCPD had lower triceps skinfold measurements (p=0.007) and mid-arm circumferences (p<0.05) compared to IDDM patients. Patients with NIDDM did not show any significant difference compared to the control group. This study shows that both FCPD and IDDM patients have lower body mass and fat mass compared to NIDDM patients and control subjects.