Failure of human insulin to influence endogenous basal insulin secretion in mild diabetics

In evaluating the possibility of self-regulation of insulin secretion in man, human insulin may be more appropriate as an inhibitor to be considered than insulins from other species because the differences in the structure of the hormones might play some part in this conflicting proposal. The present study was carried out to examine whether human insulin per se can exert a feedback effect on the insulin secretion of B-cell in mild diabetics under physiologic condition. Fifteen mild diabetics were given a two-hour infusion of human insulin at a constant rate of 40 mU/m/min after a priming dose of 160 mU/m/min for the first two minutes. The plasma glucose in nine of these patients were maintained at their basal level of 92.8 +/- 3.7 mg/dL (Group A) with a glucose clamp technique (the coefficient of variation = 5.0 +/- 0.8% during the clamp), while that in the remaining six patients were intentionally altered, within physiologic range, from 114.5 +/- 8.4 mg/dL to 83.8 +/- 4.9 mg/dL (Group B). During insulin infusion the plasma immunoreactive insulin (IRI) level were well-maintained at about 50 microU/mL level in both groups, whereas the C-peptide reactivity (CPR) in group B decreased from 1.28 +/- 0.15 ng/mL to 0.59 +/- 0.14 ng/mL in parallel to the change of plasma glucose, in contrast to the relatively stable CPR level of 0.92 +/- 0.08 ng/mL in group A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Symptoms and incidence of hypoglycemia in 100 insulin dependent diabetics

The aim of this study was to discover the frequency and the symptoms of hypoglycaemic reaction and coma. One hundred type I diabetic patients answered an oral questionnaire and explained how they were awaken from their hypoglycaemicoma. The frequency of hypoglycaemic reaction was from one a day to one a year. 41 patients had nocturnal hypoglycaemic reactions. Our patients described 27 different symptoms of oncoming attack; however, not all of these symptoms was experienced by any one of the patients. Treatment of hypoglycaemic reaction was administered correctly but at the precise moment of the interview, 13% of patients had no carbohydrates with them. 42 patients had had hypoglycaemic reaction but no coma. Shared between 48 patients were 578 insulin years and 148 comas. Treatment of hypoglycaemic coma was variable: 20 patients remained at home receiving appropriate treatment; 33 were always hospitalised on attack and 20 were still comatous on each admission. The explanation of hypoglycaemic attack was variable; an emotional factor was given by 19% of patients. Both type I diabetic patients and their immediate entourage should be made aware of all the symptoms of oncoming attack and of the treatment of hypoglycaemic coma. Systematic glycemic auto control should testify to the existence of genuine hypoglycaemic reaction and perhaps diminish its supposed frequency.     

Calcium and phosphorus metabolism in insulin dependent and non-insulin dependent diabetics, well-controlled and poorly-controlled

We studied phosphorus and calcium metabolism in 50 adult insulin dependent and non insulin dependent diabetics arranged in 4 groups according to therapy and control of diabetes. We observed: a low level of blood magnesium in all diabetics a lower level of P T H, more pronounced with poorly controlled diabetes. a decrease of 1-25 (OH) 2 D levels without modification of the 25 (OH) D levels in badly controlled diabetics. This decrease may be related to the low level of PTH with a 1 alpha hydroxylation defect. These results are in favor of the hypothesis of a primary bone problem leading to the pre-senile and subclinical osteoporosis observed in diabetics. Hyperglycaemia rather than insulinopenia may be involved. Rigorous diabetes control significantly decreases all the observed differences, except the low magnesium level.     

Factors affecting E-rosette forming ability in peripheral lymphocytes of insulin dependent diabetics

Summary Poorly controlled insulin dependent diabetics showed impaired E-rosette forming ability compared to sex and age matched normal controls (34.8±3.1, n=31 vs 55.5±1.7, n=33; p< 0.001; mean±SEM). The reduction of E-rosette cells % was not related to the duration of diabetes, nor to fasting blood glucose levels. Incubation of lymphocytes from a subsequent series of 17 insulin-dependent diabetics with insulin (100 U/ml) plus glucose (100 mg/100 ml) significantly increased E-rosette formation (37.6±3.3 vs 47.0±2.2; p= 0.01); conversely glucagon (0.1 g/ml) significantly impaired E-rosette forming ability of normal lymphocytes (51.5±3.6 vs 44.5±4.2; n=17; p< 0.01). No difference was observed in cAMP content of normal and diabetic lymphocytes, nor was E-rosette forming ability related to intracellular cAMP content. Incubation with increasing glucose concentrations (up to 500mg/100ml) did not affect E-rosette forming ability of normal lymphocytes. Incubation of normal lymphocytes with diluted (110) serum from sex and age matched insulin dependent diabetics impaired E-rosette forming ability to the level found in diabetics (61.1 ± 2.9 vs 39.7 ± 4.4; p < 0.001). The results of these in vitro experiments show that insulin and glucagon exhibit opposite effects on E-rosette forming ability and that undefined factor(s) present in diabetic serum may affect this T-cell function.     

Platelet aggregation and coagulation factors in insulin dependent diabetics with and without microangiopathy

Abnormalities of platelet aggregation and coagulation have been reported in insulin dependent diabetes mellitus (IDDM), although there is controversy concerning their relationship to microangiopathy. We have studied platelet function and haemostasis in 55 patients with IDDM, 23 without, 14 with mild (background retinopathy) and 18 with severe (proliferative retinopathy, or background retinopathy plus proteinuria) complications. Studies were done on 2 occasions 8 weeks apart and the results compared with 28 control subjects. There was evidence of increased in vivo platelet aggregation in the diabetic group v controls shown by raised values of beta-thromboglobulin (61 +/- 42, mean +/- SD, v 18 +/- 14 micrograms/ml, p less than 0.001), platelet factor 4 (62 +/- 76 v 14 +/- 11 micrograms/ml, p less than 0.01), and platelet micro-aggregates (20 +/- 16 v 12 +/- 11%, p less than 0.01). There was no significant difference in fibrinogen and fibrinopeptide A levels, nor in 'in vitro' tests of platelet aggregation between the groups. Dilute whole blood clot lysis time was increased in the diabetic group v controls (6.4 +/- 2.6 v 4.8 +/- 0.5 hours, respectively, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

B-cell function and blood glucose control in insulin dependent diabetics within the first month of insulin treatment

Summary Seventeen insulin dependent diabetics were studied after two to four weeks of insulin treatment in a situation approximating to their normal daily life. Some endogenous insulin secretion, assessed by plasma C-peptide determinations, was present in all. Plasma C-peptide concentration was positively correlated with the blood glucose concentration and increased after breakfast, lunch and dinner (p<0.01); both peak values and relative increases were lower than those observed in normal subjects (p<0.01). The highest insulin secretory capacity was found in subjects with the least unstable blood glucose concentration (r=0.57, p <0.03), and these patients required the smallest insulin doses (r=0.54, P<0.04). These findings demonstrate the metabolic importance of a preserved B-cell function.     

Evidence of early impairment of parasympathetic reflexes in insulin dependent diabetics without autonomic symptoms

Cardiovascular (CV) autonomic functions were assessed in 50 insulin-dependent diabetic patients and in 30 controls using a battery of autonomic tests: Valsalva Manoeuvre (VR), Deep Breathing (DB), Lying-to-Standing (LS), Sustained Handgrip (SHG) and Postural Hypotension (PH). The results were compared with those obtained from a study of cardiac resting adjustment to different static postures (quiet lying and standing). 10 diabetics with abnormal responses to the majority of tests were considered affected by Diabetic Autonomic Neuropathy (DAN); 15 with some abnormal of borderline responses were defined much less than Borderlines much greater than. The remaining 25 diabetics, while displaying lower values than the controls in parasympathetic tests, had much less than normal much greater than autonomic responses. The VR mean (+/- SD) value was 1.71 +/- 31 in much less than normal much greater than diabetics and 2.01 +/- 0.29 in controls (p less than 0.001); the DB mean value was 20.6 +/- 87 and 28 +/- 8.13 (p less than 0.001), and the LS mean value 1.16 +/- 0.12 and 1.33 +/- 0.18 (p less than 0.001) respectively. No significant differences were found in the sympathetic tests (SHG, PH). However Heart Rate (HR) adjustment of diabetics with normal CV responses to immobile standing (RR mean 783 +/- 136 ms) and lying (RR mean increment of 25 +/- 11%; p less than 0.001) was similar to that of controls who had a resting HR standing (RR mean 749 +/- 104 ms) and lying (RR mean 884 +/- 116 ms) with a mean increment of 20.2 +/- 10.9% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors associated with basal insulin dose in Japanese children and young adult type 1 diabetics

Aims/Introduction: The daily basal insulin doses/body weight and the daily basal insulin doses/total daily insulin doses of Japanese type 1 diabetes mellitus patients are less than those of Western type 1 diabetes mellitus patients. It is known that Western meals are richer in fat than Japanese meals. We speculated that fat intake might be associated with basal insulin dose in type 1 diabetes mellitus patients. Materials and Methods: Forty‐one outpatients with type 1 diabetes mellitus (20 males, 21 females, mean age 15.9) were enrolled. Variables investigated included: gender, SDS‐BMI, HbA1c, duration of diabetes, therapy (MDI or CSII), insulin doses and meal contents. Meal contents were recorded for 3 days using a digital camera. Correlation and multiple regression analyses were performed for all subjects and each age group. Results: The mean daily basal insulin doses/total daily insulin doses was 0.35. In the multiple regression analysis among all subjects, when daily basal insulin doses/body weight was used as a dependent variable, fat energy ratio of the meal was obtained as an entered variable (P = 0.001). This tendency was particularly strong among the patients aged 14 or above (P < 0.001, standardized coefficient β = 0.683). Conclusions: In the type 1 diabetes patients who are aged 14 or above, an association between daily basal insulin doses/body weight and fat energy ratio of meal was suggested. This may explain the aforementioned expectation of increased fat intakes making higher basal insulin doses. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00171.x, 2011)     

Basement membrane thickness,insulin antibodies and HLA-antigens in long standing insulin dependent diabetics with and without severe retinopathy

The study was designed to show whether there was any relation between muscle capillary basement membrane thickness, HLA-antigens, anti-insulin antibodies and proliferative retinopathy. Electron microscopic measurements of muscle capillary basement membrane thickness were performed on muscle biopsies from 15 insulin-dependent diabetics and severe proliferative retinopathy, 24 insulin-dependent diabetics with minimal retinopathy and 18 age- and sex matched non-diabetics. All the patients had had diabetes for 20 years or more. None had biochemical or clinical evidence of diabetic nephropathy. Basement membrane thickness was measured according to the methods of Siperstein and Williamson. Muscle capillary basement membrane thickening occurred in 32 of 39 diabetics, using the Siperstein method, but patients with proliferative retinopathy did not exhibit thicker basement membranes than patients with no or minimal changes in the retina. There were apparent differences in HLA-antigens between diabetics with and without proliferative retinopathy, but they did not reach statistical significance. There was no correlation between muscle capillary basement membrane thickness and the quantity of insulin antibodies. The results indicate that factors other than basement membrane thickening and genetic factors in the HLA-region, are responsible for the development of proliferative retinopathy.     

Characteristics of basal insulin requirements by age and gender in Type-1 diabetes patients using insulin pump therapy

Establishment of appropriate basal insulin levels is an essential component of intensive insulin therapy. While the existence of a "dawn phenomenon" is widely recognized, the present study sought to establish whether diurnal basal insulin patterns exist in Type-1 diabetes, and whether these patterns vary by age and gender. Participant data was drawn from 322 Type-1 insulin pump users treated at a private diabetes education practice in suburban Philadelphia. All participants completed a battery of fasting tests designed to match basal insulin levels to endogenous glucose production and insulin sensitivity. Analysis of resultant basal patterns revealed significant differences between juvenile (age < or =20) and adult (age >20) basal insulin patterns. The younger group exhibited a more pronounced and sustained night-time peak; the older group exhibiting a briefer and less pronounced early-morning peak. Lower overall basal insulin requirements were found in the youngest (age < or =10) and oldest (age >60) groups. No noteworthy gender differences were found. Results can serve as a guide for clinicians when initiating and fine-tuning patients who utilize basal/bolus insulin therapy.     

Prevalence of diabetes mellitus,coronary heart disease and hypertension in the families of insulin dependent and insulin independent diabetics

Summary During an epidemiological study concerning the fate of diabetics in Warsaw, 2,356 subjects (aged 35–68 years with duration of diabetes mellitus of 3–11 years) were investigated with particular relevance to the presence of diabetes mellitus, coronary heart disease, and hypertension in their parents and siblings. Diabetics were classified into the following groups: insulin dependent, insulin independent nonobese, insulin independent obese, and a group in whom the distinction between insulin dependence and insulin independence was unclear. The findings in these groups were compared with the frequencies of these diseases in a random sample of the general population. There was an excess of diabetes in close relatives of all the diabetic groups. This was highest for insulin independent non-obese diabetics. There was no difference in the prevalence of coronary heart disease and hypertension in close relatives of insulin dependent diabetics when compared with the general population, but these were twice as prevalent in close relatives of the insulin independent non-obese group. Obese insulin independent diabetics reported a similar excess of coronary heart disease and hypertension in siblings, but the excess was less marked in parents. The prevalence of these diseases in families of probands with unclassified diabetes was intermediate between the other two groups. These results demonstrate an aggregation of diabetes mellitus with coronary heart disease and hypertension in families of insulin independent non-obese diabetics. This provides further evidence for heterogeneity in diabetes mellitus.     

The effect of hyperglucagonaemia on blood glucose concentrations and on insulin requirements during fasting in insulin dependent diabetes mellitus

The effect of sustained hyperglucagonaemia on blood glucose concentrations and on insulin requirements was evaluated in 6 fasting insulin dependent diabetic subjects whose blood glucose concentrations were being controlled with a closed loop insulin infusion system. Subjects were iv infused initially with either saline or glucagon and subsequently with the other infusate. All determinations were performed following the period during which transient increases in glucagon stimulated glucose production have been reported to occur. Plasma glucagon concentrations were significantly higher during the glucagon study period (491 +/- 65 vs 70 +/- 13 pg/ml +/- SD, P less than 0.001) as were blood glucose concentrations (104 +/- 2 vs 84 +/- 7 mg/ml +/- SD, P less than 0.001) and insulin requirements (3.5 to 36.5 vs 0 to 2.3 mU/kg/h, P less than 0.05). Sustained hyperglucagonaemia continues to have an effect on glucose homeostasis for at least 2 h following the initiation of a continuous infusion.     

甘精胰岛素加三餐前短效胰岛素和胰岛素泵短期强化治疗对2型糖尿病疗效比较

目的探讨甘精胰岛素联合三餐前短效胰岛素和胰岛素泵治疗对口服降糖药效果不佳的2型糖尿病的疗效、安全性及性价比。方法60例T2DM患者分为甘精胰岛素注射（甘精组）和胰岛素泵（CSII组）,两组的年龄、BMI、FDP、FPG、2hC-P、2hPG、HbA1C差异无统计学意义（P〉O．05）。结果甘精组和CSII组治疗均有效,FPG、2hPG均较治疗前明显下降,FC-P、2hC-P均较治疗前明显升高（P〈0．05）。两组达到相同血糖水平所需的治疗时间以及低血糖发生率无统计学差异（P〉O．05）,但甘精组的胰岛素用量明显低于CSII组（P〈0．05）。结论甘精胰岛素配合三餐前短效胰岛素能有效模拟人生理胰岛素分泌,有效控制高血糖,且效价比高于胰岛素泵。     

Improvement of metabolic control in insulin dependent diabetics treated with the α-glucosidase inhibitor Acarbose for two months

Summary Acarbose, an -glucosidase inhibitor, delays starch digestion and inhibits intestinal sucrase and maltase activity. Twenty-eight insulin dependent diabetics were given Acarbose (3×100 mg daily) over a two month period, preceded and followed by a two month placebo period. Acarbose reduced post-break-fast and post-dinner blood glucose values by 25% (p <0.001) and 24% (p<0.05) respectively. It also significantly reduced mean daily blood glucose by 18% (p < 0.05) and mean amplitude of glycaemic excursions from 8.0±0.6 to 5.5±0.4 mmol/l (p<0.0005). Weight did not change significantly. Daily caloric and carbohydrate intake remained constant throughout the study while insulin requirements decreased slightly but significantly. Out of the 28 patients, 18 had absent while ten had slight residual B cell function as assessed by plasma C-peptide measurements. Treatment with Acarbose did not significantly affect residual B cell function. The beneficial effect of Acarbose on blood glucose control was seen in patients both with and without residual B cell secretion. The major side-effect was flatulence which was never severe enough to interrupt treatment, but led to a 50% reduction of the dose in one patient. It is concluded that Acarbose represents a useful additional means of improving metabolic control in insulin dependent diabetics.     

Prandial insulin requirements in insulin-dependent diabetics: effects of size, time of day, and sequence of meals

To assess the effects of size, time of day, and sequence of meals on insulin requirements determined by an artificial endocrine pancreas, eight insulin-dependent diabetics ate meals of 12.5%, 25%, and 50% of total calories (30 Kcal/kg) at 0800, 1300, and 1800 on each of 3 separate days in a randomized order in one of two sequences in a three by three Latin square design. Plasma glucose and free insulin concentrations and amounts of insulin infused by the artificial endocrine pancreas were associated with meal size (P less than 0.001) but not with time of day of meal ingestion (analysis of variance). The sequence of meal ingestion did not alter integrated plasma glucose responses, but did influence the meal-related amounts of insulin infused. Thus, consideration should be given to meal size and sequence of meal ingestion but not time of day of meal ingestion when determining prandial iv insulin requirements.     

Combination treatment of insulin dependent elderly diabetics (type II diabetes) with the sulfonylurea compound glibenclamide

About 20 per cent of our patients between sixty and eighty years suffer from maturity onset diabetes including many subjects with an insulin requiring form. Beside cases of secondary failure were those with increased insulin resistance. In order to improve low compliance, a clear therapy is desirable. Therefore a combination of sulfonylurea with insulin is suitable instead of a repeated insulin-delivery by day. This way of treatment is known since the late fifties and its application increases in the last years. These results suggest that a combination with glibenclamide leads to a decrease of insulin-requirement. This is true both for secondary failure and difficult insulin monotherapy. More than 80 per cent of those patients who needed a twice by day insulin injection now do with only one delivery. The course of daily blood sugar profile is clearly smoothed.