Ambulatory 24-hour fast using flexible insulin therapy in patients with type 1 diabetes.

AIM: Prolonged fasting may be necessary in life for religious, medical and other reasons. For this reason, our study investigated the feasibility and safety of a 24-h fast conducted at home for patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Thirty-four patients with type 1 diabetes performed a 24-h complete fast at home. Thirteen patients were treated with multiple insulin injections using either glargine (n=12) or NPH (n=1) as basal insulin. The remaining patients were treated with an insulin pump. All patients received their basal insulin only, which was adjusted to 40% of their total daily dose, and were monitored by either a Gold(®) or Guardian(®) continuous glucose monitoring (CGMS) device. Capillary glucose (SMBG) was targeted at 3.9-7.8 mmol/L, with a standardized protocol for correction of hyper- and hypoglycaemia. Interstitial glucose (IG) profiles were compared with the SMBG values; the IG profiles of patients using glargine or a pump and either of the two CGMS devices were also compared. RESULTS: All of the patients completed the 24-h fast with no major incident. At the end of the fast, 80% of the IG values were on target. The route by which insulin was delivered made no difference, but there were more IG values on target in patients monitored by the Guardian(®) device. IG was below target in 104 occurrences and above-target in 34. After a mean intake of 10 g of sucrose, below-target IG was corrected within 30 min [range: 15-40]. The mean insulin dose to correct above-target episodes was 1 U. CONCLUSION: Prolonged fasting is possible at home in patients with type 1 diabetes, provided the basal dose is adjusted. The use of CGMS is not necessary, but offers useful information on the patient's IG profile during the fast.

Peak-time determination of post-meal glucose excursions in insulin-treated diabetic patients.

OBJECTIVE: This study aimed to determine the optimal time to measure peak blood glucose values to find the best approach for self-monitoring blood glucose after a meal. DESIGN AND METHODS: For this retrospective analysis, 69 ambulatory continuous glucose-monitoring system (CGMS) profiles were obtained from 75 consecutive insulin-treated patients with diabetes. The parameters measured were the peak post-meal blood glucose values, peak time, and rates of increase and decrease to and from the zenith of the resulting curves. RESULTS: The mean peak time after breakfast was 72+/-23 min, which was reached in less than 90 min in 80% of the patients. The apparent glucose rate of increase from pre-meal to the maximum postprandial value was 1.23+/-0.76 mg/dL/min, while the glucose rate of decrease was 0.82+/-0.70 mg/dL/min. Peak time correlated with the amplitude of postprandial excursions, but not with the peak glucose value. Also, peak times were similar after breakfast, lunch and dinner, and in type 1 and type 2 diabetic patients. CONCLUSION: To best assess peak postprandial glucose levels, the optimal time for blood glucose monitoring is about 1h and 15 min after the start of the meal, albeit with wide interpatient variability. Nevertheless, 80% of post-meal blood glucose peaks were observed at less than 90 min after the start of the meal.

Prevalence and predictive factors of sleep apnoea syndrome in type 2 diabetic patients.

AIM: This study aimed to assess the prevalence and characteristics of sleep apnoea syndrome (SAS) in patients hospitalized for poorly controlled type 2 diabetes. METHODS: An overnight ventilatory polygraphic study was systematically performed in 303 consecutive patients. RESULTS: Overall, 34% of these patients had mild SAS, as defined by a respiratory disturbance index (RDI) of 5-15; 19% had moderate SAS (RDI: 16-29) and 10% had severe SAS (RDI>or=30). The SAS was obstructive in 99% of the apnoeic patients. The percentage of patients with excessive daytime sleepiness (Epworth sleepiness scale>10), fatigue or nocturia did not significantly differ among patients with severe, moderate or mild SAS versus non-apnoeic patients. The percentage of patients who snored was significantly higher in patients with severe or moderate SAS versus non-apnoeic patients. HbA(1c), duration of diabetes and the prevalences of microalbuminuria, retinopathy and peripheral neuropathy did not significantly differ among patients with severe, moderate or mild SAS versus non-apnoeic patients. However, patients with severe or moderate SAS had significantly higher values for body mass index, waist circumference and neck circumference than non-apnoeic patients. CONCLUSION: In type 2 diabetic patients with poor diabetic control, obstructive SAS is highly prevalent and related to abdominal obesity, and should be systematically screened for, as it cannot be predicted by the clinical data.

Circulating platelet-leukocyte aggregates: a marker of microvascular injury in diabetic patients.

Diabetes is associated with multiple disorders including metabolic, cellular and blood disturbances leading to vascular complications. Increased circulating levels of platelet-leukocyte aggregates (PLA) have been described in several thrombotic diseases. In this study, we have evaluated circulating PLA in diabetic patients and we have investigated whether they may be a marker of vascular complications. Using flow cytometry assay, we have quantified PLA percentages in 65 diabetics including 20 patients with type I and 45 with type II diabetes, and 25 healthy subjects. Specific labelling identified platelet-polymorphonuclear aggregates (PPA) and platelet-monocyte aggregates (PMA). We have observed a significant increase of PPA and PMA levels in diabetics (22+/-12% and 45+/-18%, respectively) compared to controls (7+/-4% and 19+/-10%, respectively) (p<0.01). However, both PPA and PMA values were similar in the two diabetes types. Circulating PPA and PMA were significantly enhanced in diabetics with vascular lesions (PPA: 24+/-13%; PMA: 50+/-18%) than in diabetics without vascular lesions (PPA: 18+/-8%; PMA: 38+/-15%) (p<0.05 and p<0.01). Patients with PPA>18% and/or PMA>38% showed a more important vascular injury (OR: 6; 95% CI: 1.6-23). Increased PMA circulating rate is particularly correlated to retinopathic injury (OR: 19; 95% CI: 2.3-154). Our findings established a relationship between increased circulating PLA levels, particularly PMA, and the incidence of microvascular complications in diabetes. They reinforce the concept of pro-inflammatory cells involvement in diabetic retinopathy pathogenesis and their link with thrombotic process.

Postprandial glycaemia: a plea for the frequent use of delta postprandial glycaemia in the treatment of diabetic patients.

Postprandial hyperglycaemia is a phenomenon often neglected by patients as well as doctors. While patients only voluntarily measure morning and preprandial capillary glycaemia, physicians do not encourage the measurement of anything further. The specific role of postprandial hyperglycaemia in the determination of late diabetes complications, such as micro- and macroangiopathy, remains controversial. It is however undeniable that the postprandial glycaemic excursion plays an important role in total hyperglycaemia reflected by an increase in glycated haemoglobin. The postprandial glycaemia measurement or, more appropriately, the postprandial glycaemic excursion (the difference between postprandial and preprandial glycaemia, also called the postprandial delta glycaemia), is important to measure and there are specific tools to correct it when abnormal. Postprandial delta glycaemia should lie between 30 and 50 mg/dl. It is thus suggested to measure it not necessarily on a daily basis, but when it is expected that the glycaemic couple, or "pre-postprandial couple", is high. The specific tools for treatment of postprandial hyperglycaemia can be dietetic (carbohydrate quantity reduction or ingestion of fiber-rich and/or low glycaemic index foods) or medicinal. Among the specific medicinal treatments are the alpha-glucosidase-inhibitors (which can be used for both type 1 and type 2 diabetic patients), glinides and fast-acting insulins. Rather than first treating fasting and interprandial hyperglycaemia, as has been commonly done by physicians, the authors recommend the simultaneous treatment of pre-, inter- and postprandial hyperglycaemia. The optimal time at which to evaluate postprandial glycaemia is approximately 1 h and 15 minutes for type 1 and type 2 diabetic patients.

Uncommon early-onset neuropathy in diabetic patients.

An acute neuropathy rarely occurs early in the course of diabetes mellitus. Five cases are described of adult patients who developed a peripheral neuropathy at the time or shortly after the onset or discovery of diabetes mellitus. Patient 1, an 80-year-old woman who developed a subacute tetraparesis with proximal and distal muscle weakness with normal cranial nerves, proved to have insulin-requiring diabetes mellitus. In the other patients, all men aged 23-34 years, symptomatic neuropathy occurred simultaneously (patient 2) or 1-6 months after the onset of insulin-dependent diabetes mellitus (IDDM) (patients 3-5). Patients 2 and 3 developed a symptomatic multifocal neuropathy; patients 4 and 5, a painful distal symmetrical sensory polyneuropathy (DSSP) shortly after beginning treatment with insulin. Nerve biopsy showed active axonal lesions in patients 2 and 5 and mixed axonal and demyelinating lesions in the others, with severe axon loss in patients 4 and 5. Vasculitic lesions were found in patient 2, who improved without additional treatment. Neurological examination remained unchanged after 2 years in patients 3-5. Although a coincidence cannot be excluded for patients 1-3, whose neuropathy was not of the pattern commonly found in diabetes, it is suggested that acute disequilibrium in the diabetic status may facilitate the occurrence of a variety of neuropathies. Alternatively, the autoimmune process which led to IDDM may also trigger an autoimmune neuropathy with vasculitis (patient 2) or demyelinative nerve lesions. Only the distal symmetrical sensory polyneuropathy with severe axonal lesions observed in patients 4 and 5 seems directly related to diabetes mellitus. In spite of their occurrence shortly after beginning insulin therapy, the role of treatment with insulin in the onset is uncertain.

Painful proximal diabetic neuropathy: inflammatory nerve lesions and spontaneous favorable outcome.

Proximal diabetic neuropathy is a disabling neuropathy that occurs predominantly in non-insulin-dependent diabetic patients over the age of 50. Inflammatory lesions have been found in nerve biopsy specimens of diabetic patients with severe proximal neuropathy or with other patterns of multifocal neuropathy. Some of these patients respond dramatically to treatment with corticosteroids or with other immunomodulators. In this article we report on our findings in 4 additional patients with painful proximal diabetic neuropathy and different patterns of inflammatory nerve lesions whose condition improved spontaneously shortly after performance of a nerve biopsy, without additional treatment.

Extreme insulin resistance: clinical management by external subcutaneous insulin infusion.

Management of very high insulin requirements in rare extreme insulin resistance syndromes is difficult and poorly documented. We report a case of a type B insulin-resistant patient requiring approximately 10,000 units of insulin per day, i.e. beyond the possibilities of current insulin formulations and delivery devices. Only the Panomat C10 portable pump model (Disetronic) and U500 Humulin (Lilly) allowed the required rate of 400 units per hour to be attained only when the reservoir was changed twice daily and the site and catheter were changed once daily. Three months after discharge, the patient was in good general and local condition, but with only fair diabetes control (glycated haemoglobin 9.5%).

Initiation of insulin treatment after 70 years of age: patient status 2 years later.

The present study assessed 106 diabetic patients 2 years after beginning insulin treatment at or after 70 years of age. Ten patients (9%) had had the therapy discontinued after 2-4 months, 26 (25%) had died of causes unrelated to insulin therapy, 12 (11%) were lost to follow-up, and 58 (55%) were still alive and insulin treated. Fifty-one were at home and seven institutionalized for reasons unrelated to insulin therapy. Of these 58 patients, 50 were available for further study. Except for frequency of travel, which had decreased, lifestyle either improved or did not change. Patients' perceptions of the goals of treatment were more appropriate to a younger population of patients, who are less vulnerable to hypoglycaemic reactions. Mean fasting blood glucose was considered by the medical staff to be too low in 42% of cases. Adding insulin to the treatment of the elderly did not negatively affect their lifestyle, and indeed, insulin therapy appeared to create or strengthen the patients' existing social support network. Educational interventions must attempt to extend the effect of the specialized unit outside the hospital, to families, visiting nurses as well as general practitioners.

A preliminary multicentre study of the treatment of recently diagnosed type 1 diabetes by combination nicotinamide-cyclosporin therapy.

The aim of the present study, a pilot trial, was to find out if nicotinamide (50 mg kg-1 day-1) in combination with cyclosporin A favours remission in recently diagnosed Type 1 diabetic patients, and if it postpones relapse even when cyclosporin A is administered in decreasing doses (trough blood level 300-500 micrograms l-1 until month 4, and 100-300 micrograms l-1 until month 9) and then discontinued. The criteria for inclusion in the study and the follow-up protocol were the same as those used in the Cyclosporin Diabetes France (CDF) programme in which all five of the centres involved in this study participated. The data of the present preliminary open study were therefore compared retrospectively with those of the placebo (CDF-placebo) and cyclosporin (CDF-active) group of the CDF programme. Clinical remission (fasting plasma glucose less than 7.8 mmol l-1, postprandial plasma glucose less than 11.1 mmol l-1, HbA1c less than 7.5% with neither insulin nor oral hypoglycaemic agents) was achieved within 6 months in 12 out of 35 patients (34%) vs 16 out of 63 (25%) in CDF-active and 11 out of 59 (19%) in CDF-placebo. Remission was achieved by month 9 in 6 out of 35 patients (17%) vs 13 out of 54 (24%) in CDF-active and 3 out of 52 (6%) in CDF-placebo. By 12 months remission persisted in 3 out of 35 patients (9%) vs 11 out of 63 (17%) in CDF-active and 0 out of 52 (0%) in CDF-placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of metformin treatment on erythrocyte insulin binding in normal weight subjects, in obese non diabetic subjects, in type 1 and type 2 diabetic patients.

We have evaluated the effects of metformin administration on erythrocyte insulin receptors in 21 subjects: 5 normal weight subjects, 5 obese non diabetics, 5 insulin-dependent diabetics (Type I) and 6 obese non insulin-dependent (Type II) diabetics. Plasma glucose, plasma insulin and erythrocyte insulin receptors were studied after 15 days of metformin (850 mg, t.d.) or placebo administered in a double blind random order. Maximum specific insulin binding to erythrocytes increased after metformin in the normals (p less than 0.01), in the obese non diabetics (p less than 0.01) and in the obese Type 2 diabetics (p less than 0.005), but not in Type I diabetics. Scatchard analysis showed that the receptor number per cell increased by 37% in the normals, by 17% in the obese non diabetics and by 182% in Type 2 diabetics. Receptor affinity increased in obese subjects but did not increase in normals and in diabetics. Only in Type II diabetics was there a significant decrease in plasma glucose. Metformin, thus, increased binding in normals by moderately increasing the capacity of cell receptors, in obese non diabetics by increasing the affinity, whereas in obese Type II diabetics it dramatically increases receptor capacity. This is consistent with the fact that metformin has a hypoglycaemic effect mainly in Type II diabetics, but not in non diabetics (whether obese or not), and could be due to a direct effect on the cell membrane.