Intracellular metabolism in patients with insulin-dependent and non-insulin-dependent diabetes mellitus

Slow infusion of neutral insulin causes in patients with insulin dependent and noninsulin dependent diabetes mellitus diverse changes in the levels of cAMP, cGMP and the cAMP/cGMP ratio in leukocytes in spite of one-type changes in the concentration of contrainsular hormones in the venous blood: in patients with noninsulin dependent DM a raised cAMP/cGMP factor was lowered whereas in patients with insulin dependent DM it was increased. The authors put forward for discussion the problem of the postreceptor mechanisms of tissue insulin resistance in noninsulin dependent DM and a possibility of the use of the above indices for differential diagnosis of DM types.     

Insulin and a sulfonylurea agent in non-insulin-dependent diabetes mellitus

Using a double-blind crossover design, we studied the effect of tolazamide, an orally administered sulfonylurea, in 11 patients with non-insulin-dependent diabetes mellitus, poorly controlled on 40 units/day or more of insulin; all had previously failed to respond adequately to oral hypoglycemic agents and diet. In addition, six nondiabetic sex-, age-, and weight-matched controls were studied. Tolazamide significantly lowered fasting plasma glucose level from 272 +/- 21 to 222 +/- 31 mg/dL, increased fasting C peptide concentration from 0.09 +/- 0.03 to 0.28 +/- 0.10 pmole/mL (controls, 0.23 +/- 0.2 pmole/mL), and increased integrated C peptide concentration during a test meal (area under the curve) from 42 +/- 18 to 95 +/- 22 pmole/mL X min (controls, 94 +/- 8 pmole/mL X min). These data show that addition of tolazamide markedly increased fasting and meal-stimulated insulin secretion and modestly lowered fasting plasma glucose concentrations. We conclude that some patients who cannot achieve satisfactory control with oral hypoglycemic agents and diet may benefit from combined therapy with oral sulfonylurea agents plus insulin.     

Comparison of renal hemodynamics in early non-insulin-dependent and insulin-dependent diabetes mellitus

The differences in deranged renal hemodynamics in non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) have never been fully investigated. Whether or not autoregulatory mechanism of renal hemodynamics in NIDDM and IDDM is preserved remains to be clarified.In the present study we directly compared renal hemodynamics and its autoregulatory function in the early stage of NIDDM and IDDM before and after short-term glycemic control. Before glycemic control, mildly exaggerated glomerular filtration rate (GFR), subnormal renal plasma flow (RPF), and elevated filtration fraction (FF) were found in NIDDM as well as in IDDM; but there were no differences in these parameters of renal hemodynamics between the two types of diabetics. Glycemic control decreased GFR, whereas it did not alter RPF, resulting in normalization of FF in NIDDM and in IDDM. Before glycemic control, mean blood pressure was significantly correlated with GFR, but was not correlated after glycemic control in either type of diabetes. In conclusion, hyperglycemia induced glomerular hyperfiltration evenly and disturbed autoregulation of renal hemodynamics in NIDDM and in IDDM.     

Digital sclerosis in children with insulin-dependent diabetes mellitus

Palpable thickening and induration of the skin of the fingers were found in 47 (34%) of 137 children with insulin-dependent diabetes mellitus and in none of 52 normal children. Mild flexion contractures of the interphalangeal joints were seen in 26 (19%), mainly in those children with more extensive and severe skin changes. Such contractures have been linked to microvascular complications of diabetes. The clinical and pathogenic similarities to progressive systemic sclerosis make the digital sclerosis of childhood diabetes a promising model for further rheumatologic study.     

Hypoglycemia in children with insulin-dependent diabetes mellitus.

The promotion of normal growth and development and the avoidance of acute and long-term complications are overall goals in the management of a child with insulin-dependent diabetes mellitus. Recent studies provide new and pertinent information about the acute effects of hypoglycemia on such cognitive functioning as learning, memory, reading, and visuospatial skills. The effects of early onset diabetes on school performance are also discussed. This information should be incorporated by diabetes educators into the educational plan for children with IDDM, their families, and schools.     

Glycosylated haemoglobin in children with insulin-dependent diabetes mellitus

Summary Glycosylated haemoglobin (HbA₁) was measured serially by microcolumn chromatography in 38 children with newly diagnosed insulin-dependent diabetes. Initial HbA₁ levels of 13.6±0.5% fell significantly from day 0 (prior to therapy) both to day 1 (1.6±0.2% decrease) and to day 3–5 (2.6±0.4% decrease) (p < 0.001). This drop correlated closely with changes in blood glucose (p < 0.001), less closely and inversely with plasma bicarbonate levels (p < 0.01), but not with prior duration of symptoms or changes in serum cholesterol and triglyceride concentrations. HbA₁ levels reached a nadir of 8.2±0.3% 3 weeks to 6 months after diagnosis, and correlated with decreasing insulin dosage (p < 0.001). HbA₁ levels rose again to 11.4±0.5% in 21 patients followed for more than 3–6 months. Our results indicate that (1) HbA₁ levels change rapidly during initial stabilization of insulin-dependent diabetes suggesting that glycosylation may not be entirely irreversible, and (2) HbA₁ levels are consistent with clinical assessment of control during remission and postremission phases.     

Anticardiolipin antibodies in children with insulin-dependent diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that selectively destroys insulin-secreting pancreatic beta cells. Anticardiolipin antibody is an autoantibody directed against cell membranes. An association of this antibody with diabetes mellitus has not been widely reported. The current investigation was performed to determine the prevalence of IgG and IgM anticardiolipin antibodies in 2 groups of children with type 1 IDDM and to find a relation, if any, with the control and duration of the disease. The study included 30 children with type 1 IDDM and 20 healthy control children. The children were subjected to history taking, clinical examination, and laboratory estimation of anticardiolipin IgG and IgM antibodies and glycosylated hemoglobin (HbA(1c)). Analysis of the results showed that the mean levels of serum anticardiolipin IgG and IgM antibodies were significantly higher among the diabetic children than the healthy controls. Mean values of serum anticardiolipin IgG and IgM antibody levels were significantly higher in children with recent-onset diabetes (29.90 +/- 12.60 GPL/mL and 12.825 +/- 3.762 MPL/mL) than in those of long duration (>1 year: 10.84 +/- 5.796 GPL/mL and 4.142 +/- 2.910 MPL/mL, respectively). A negative correlation between the duration of diabetes and the level of IgG and IgM anticardiolipin antibodies and a positive correlation between the level of IgG and the level of IgM antibodies were observed. However, there was a nonsignificant correlation between anticardiolipin IgG and IgM levels and HbA(1c) levels, insulin dose, and fasting blood sugar. Therefore, anticardiolipin antibodies should be added to the list of autoantibodies detected in IDDM especially in the early stage of the disease.     

Insulin receptor binding to monocytes and erythrocytes in gestational diabetes

Insulin receptor binding to monocytes and erythrocytes was measured at the time of diagnosis and again postpartum in 23 normal weight gestational diabetics. In 16 women, insulin receptor binding was studied after a period of dietary treatment. In patients diagnosed early in pregnancy, an increase in insulin binding to both monocytes and erythrocytes was observed during dietary treatment (p less than 0.001), while no similar changes were observed in patients diagnosed later in pregnancy. Postpartum, insulin receptor binding to erythrocytes decreased in all women compared to the time of diagnosis (p less than 0.01) while insulin binding to monocytes either decreased (p less than 0.001) or remained unchanged depending on the time of diagnosis. Insulin binding was similar in those women who remained glucose intolerant and those who returned to normal glucose tolerance postpartum. The findings indicate that factors other than insulin receptor binding are involved in the pathogenesis of gestational diabetes.     

Insulin resistance following nocturnal hypoglycaemia in insulin-dependent diabetes mellitus

Glucose metabolism was studied by a somatostatin-insulin-glucose infusion test (SIGIT) for 8 h in 7 male patients with insulin-dependent diabetes mellitus. They were investigated on two occasions in random order, with and without preceding hypoglycaemia induced between 3.00 and 4.00 h. SIGIT was started at 7.00 h when blood glucose was restored to normal and the counterregulatory hormones had returned to basal values. As expected, hypoglycaemia evoked an enhancement of the plasma levels of GH (43.7 +/- 10.1 vs 4.4 +/- 1.8 micrograms/l), cortisol (690 +/- 59 vs 140 +/- 32 nmol/l), glucagon (225 +/- 35 vs 143 +/- 25 ng/l), and epinephrine (3.80 +/- 1.00 vs 0.10 +/- 0.03 nmol/l). During the SIGIT, the levels of circulating free insulin and counterregulatory hormones were similar in the two tests notwithstanding that excessive hyperglycaemia appeared when SIGIT was preceded by hypoglycaemia. The present study thus demonstrates that nocturnal hypoglycaemia induces insulin resistance in insulin-dependent diabetic patients not deprived of insulin.     

Insulin autoantibodies and insulin-induced antibodies in children with insulin-dependent diabetes]

AIM OF THE STUDY: The aim was to study the time course of development of insulin antibodies during the first months of treatment in diabetic children, under human insulin therapy, and to see whether the presence of insulin autoantibodies influenced the subsequent binding to insulin. METHODS: Anti-insulin antibodies were measured using a radio-binding assay in 16 diabetic children, aged 4-13 years, before the first insulin injection and at regular intervals until the 9th month of treatment. RESULTS: Insulin autoantibodies were detected in 11 out of the 16 children at the time of diagnosis. Binding to insulin increased significantly after one month of treatment in these children, and after 2 months in the children with no insulin autoantibodies at diagnosis. After 2 months insulin therapy, all the children demonstrated antibodies against insulin. Insulin binding at 9 months was not correlated to the baseline values. Anti-insulin antibodies develop rapidly and frequently under human insulin, and are not influenced by the presence of insulin autoantibodies.     

Chronic pancreatitis and diabetes mellitus: A retrospective analysis of 156 ERCP investigations in patients with insulin-dependent and non-insulin-dependent diabetes mellitus

Background: Pancreatic exocrine dysfunction has been described frequently in IDDM and NIDDM patients. Most authors tried to explain this finding as a diabetic complication. On the other hand, diabetes secondary to chronic pancreatitis (CP) might be more common than believed so far. Aim of the Study: In this study we evaluated pancreatograms of patients with known diabetes mellitus in order to detect ductal morphology changes characteristic for CP. Methods: Consecutive diabetic patients admitted for ERCP for different reasons were evaluated retrospectively concerning ERCP findings, especially pancreatic duct changes (Cambridge classification), diabetes type, duration and therapy. Results: 156 patients (76 male, 80 female; mean age 60 years (19-93)) were studied (38 IDDM; 118 NIDDM). Pancreatic ducts were classified as normal in 23.3%, CP°I in 22.7%, CP°II in 32.7% and CP°III in 21.3%. The duct changes did not correlate with diabetes type (p = 0.19), diabetes duration (p = 0.38), diabetes therapy (p = 0.5) or age (p = 0.48). Conclusion: Since CP should be defined by morphological and functional changes, it must be concluded that a substantial number of patients with a primary diagnosis of diabetes mellitus may have CP as a concomitant disease or, more likely, as a cause for their diabetic state.     

Blood levels of alloxan in children with insulin-dependent diabetes mellitus

Alloxan is a well-known and universally used agent for evoking experimental diabetes through its toxic effect on the B cells of the Langerhans islets. In our study, blood levels of alloxan in children with insulin-dependent diabetes mellitus were investigated. The observations were made in 68 children aged 6–15 years and in a control group of 44 healthy children in the same age range. Alloxan levels were estimated spectrophotometrically. The mean level of alloxan in blood from children with insulin-dependent diabetes mellitus was 8.76±9.64 g/ml and in blood from healthy children was 1.53±1.10 g/ml. The difference was statistically significant (P<0.05). The metabolism of alloxan leads to the production of free superoxide radicals which, as is well known, injure cells and cause conditions conducive to the occurrence of diseases from autoimmunity. The results obtained suggest therefore that higher levels of alloxan in diabetic children are of significance in the onset of insulin-dependent diabetes mellitus.     

Altered adrenal and thyroid function in children with insulin-dependent diabetes mellitus

In 129 children, aged 12.6±3.8 years, affected by type 1 diabetes mellitus, the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T₃, fT₃, T4, fT4, rT₃, TSH, cholesterol, and triglycerides were evaluated and compared with those of a control group of 458 healthy age-matched children. The results were also correlated with hemoglobin HbA_1C. The DHEAS-standard deviation score (DHEAS-SDS; –0.36±0.77) was significantly different from zero in diabetic children, while the cortisol serum level was higher than in control subjects (485±94 vs 359±132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated negatively with HbA_1c. Diabetic patients also showed lower T₃ values (2.22 ± 0.4 vs 2.32±0.3 nmol/l) and a higher rT₃/T₃ ratio (0.17±0.09 vs 0.15±0.05) than controls. There was a negative correlation between T₃ and HbA_1C. Cholesterol (4.77±1.08 vs 4.51±0.76 mmol/l) and triglycerides (0.82 ±0.53 vs 0.63±0.37 g/L) levels were higher in diabetic children and positively correlated with HbA_1c, but not with DHEAS-SDS. We can therefore conclude that diabetes, particularly if poorly controlled, tends to induce a dissociation of cortisol and DHEAS secretion and a low T₃ syndrome, similar to that seen in other illnesses.     

Prevalence of insulin-dependent diabetes mellitus in Asian children

A survey was conducted in 1984-85, within Leicester City boundaries, which contains 64,535 children below the age of 15 years (20,267 Asian and 44,268 White Caucasian) to ascertain the prevalence of insulin-dependent diabetes mellitus (IDDM) using a central register maintained for the changeover to U-100 insulin, diabetic health visitor index cards, hospital admissions of diabetic children, and individual registers maintained by us. Overall prevalence per thousand for children aged 0-15 years was 0.54 for Asian and 0.99 for White Caucasians; for ages 10-15 years they were 0.97 and 1.87, and for ages 0-9 years, 0.31 and 0.38, respectively. This was not statistically different at the 5% level. Ours is the first population based study of its kind in Asian children, and challenges the view that there is a large difference in the prevalence of IDDM between Asians and White Caucasians. A wider analysis of this observation incorporating a large population base is suggested.     

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.     

Insulin therapy in insulin-dependent (type I) diabetes mellitus.

Intensive insulin therapy is suitable for individuals who want optimal glucose control and the least fluctuation in glucose levels. It permits a greater flexibility in life style and the opportunity to vary, within certain limits, meal and exercise schedules and meal content. This therapeutic approach is modeled on physiologic insulin secretion, but shortcomings in the subcutaneous route of delivery hamper the ability to control precisely the glucose levels. The therapy is most successful when the user is motivated to do the glucose monitoring and carbohydrate counting and educated to make rational decisions about how to adjust the insulin doses.