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.

Benefits of Ophdiat, a telemedical network to screen for diabetic retinopathy: a retrospective study in five reference hospital centres.

AIM: One objective of Ophdiat, a telemedical network using digital non-mydriatic cameras in Ile-de-France, is to develop a comprehensive screening programme that provides access to annual fundus examinations to all diabetic patients. The aim of this study was to evaluate the benefits of this programme in a hospital setting. METHODS: A retrospective analysis of 500 case reports of diabetic patients hospitalized before and after Ophdiat setup was performed in five reference hospital centres. At each centre, 100 case reports (50 before, 50 after) of patients aged greater than 18 years, hospitalized for their annual check-up, with no known diabetic retinopathy (DR) before hospitalization and with the last fundus examination performed greater than 11 months previously, were randomly selected. The primary endpoint was the proportion of patients whose fundus examinations were performed during hospitalization; secondary endpoints were the number of cases of DR found and the time taken by ophthalmologists to make the diagnosis. RESULTS: The mean proportion of patients with fundus examinations was 50.4% and 72.4% before and after, respectively, Ophdiat (P<0.01). The prevalence of DR was 11.1% before and 12.7% after (not significant). The mean time taken by an ophthalmologist per diagnosis of DR was 0.90 half-day before and 0.32 half-day after Ophdiat. CONCLUSION: This evaluation shows that Ophdiat, combined with the availability of modern and effective devices, has improved DR screening in diabetology departments in hospitals. Additional human resources would certainly ensure more effective use of the system.

Effects of dipeptide administration on hypoglycaemic counterregulation in type 1 diabetes.

OBJECTIVES: To investigate if a dipeptide made of glutamine and alanine is able to contribute to the recovery from insulin-induced hypoglycaemia in type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifteen adult type 1 patients were randomly assigned to study group (n=7): intravenous infusion of 20 g Dipeptiven in normal saline (i.e., 8 g alanine and 13 g glutamine), or control group (n=8): same infusion, normal saline only. A 150 min gradual hypoglycaemic hyperinsulinemic clamp was administered after 2 h of infusion. Counterregularory hormones, symptoms, and cognitive function (4 choice reaction test) were regularly measured during the study. RESULTS: Blood glucose and glucose infusion rates were similar in the 2 groups. Circulating levels of alanine and glutamine peaked at 90 min and remained elevated throughout the test. This was associated with significant differences in: glucagonemia 107 +/- 20 vs 58 +/- 8 pg/ml, and neuroglycopenic symptoms scores: 7 +/- 3 vs 18 +/- 13, at t 150 min, in study and control group, p<0.05. Dysautonomic symptoms, cognitive tests as well as epinephrine, norepinephrine, cortisol and growth hormone were similar between groups. CONCLUSION: Intravenous infusion of a dipeptide made of alanine and glutamine is capable to reactivate glucagon secretion during insulin-induced hypoglycaemia and to reduce hypoglycaemic symptoms.

Insufficient adaptation of hypoglycaemic threshold for cognitive impairment in tightly controlled type 1 diabetes.

UNLABELLED: It is well known that hypoglycaemic thresholds for hormones and symptoms occur at lower plasma glucose levels in patients with strict glycaemic control. However, whether the threshold for cognitive impairment also shifts is still an unresolved question. We studied 19 type 1 diabetic patients, including 8 with hypoglycaemia unawareness, aged 37.0 +/- 7.4 y.r., with diabetes duration 15.2 +/- 10.7 yr, and HbA1c 7.6 +/- 1.1%. Hypoglycaemic thresholds for hormones, symptoms, awareness and cognitive function using the 4-choice reaction time test (4RT), were measured every 30 min during a 150 min stepped 4.4 to 2.2 mM hypoglycaemic hyperinsulinemic clamp. We found that 4RT- accuracy deteriorated earlier than 4RT-time (3.2 and 2.7 mM, respectively, p<0.01), and that both correlated poorly with HbA1C before and after adjustment for age and diabetes duration (r=0.11, and 0.18, respectively). On the opposite, adrenaline, autonomic and neuroglycopenic symptoms, and awareness significantly correlated with HbA1c values (r=0.56, 0.70, 0.61, and 0.63, after adjustment, respectively). Furthermore, after allocating the patients into two subgroups according to HbA1c values (<8% n=12, and >=8% n=7), we found that, as opposed to other thresholds, accuracy and 4RT-time were minimally and not significantly influenced by glycaemic control, therefore exhibiting the smaller glucose thresholds shifts (- 0.2 and - 0.5 mM for accuracy and time, respectively, vs. 0.6 -0.8 for other thresholds). IN CONCLUSION: 1) the hypoglycaemic thresholds for cognitive dysfunction shift with strict glycaemic control, but not significantly and less than other thresholds, 2) as opposed to other reports, accuracy deteriorates earlier than speed during the 4RT test, and 3) these "maladapted" reactions may contribute to the higher risk for severe hypoglycaemia in subjects with tight glycaemic control.

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%).

Symptoms, hormones, and glucose fluxes during a gradual hypoglycaemia induced by intraperitoneal vs venous insulin infusion in Type I diabetes.

Intraperitoneal (IP) insulin infusion with programmable implantable pumps is associated with a reduction in hypoglycaemic events when compared to intensive diabetes management with subcutaneous insulin in patients with Type 1 diabetes mellitus. The mechanism may involve more physiological insulin kinetics, lower peripheral insulin levels or a specific hepatic action of portal insulin on hypoglycaemic counter regulation. To investigate the latter two hypotheses, we performed two hypoglycaemic clamps (controlled blood glucose decrement to 2.2 mmol l-1) in random order in 12 Type 1 diabetic patients. Insulin was infused either IP or IV for 150 min, at rates chosen to generate similar peripheral insulin levels (1 mU/kg-1 min-1 IV or 2 mU/kg-1 min-1 IP, n = 6) to evaluate direct hepatic action, or at similar rates (1 mU/kg-1 min-1 IV and IP, n = 6) to evaluate IP indirect effects via lower peripheral insulinaemia. Hepatic glucose production and glucose utilization were measured by [6.6 2H] glucose dilution technique. Glucose production was lower (1.7 +/- 0.4 vs 0.5 +/- 0.4 mg kg-1 min-1, p < 0.05), and utilization was similar at the end of the matched-insulinaemia IV and IP clamps, respectively. By contrast, glucose production was higher (1.7 +/- 0.5 IV vs 2.7 +/- 0.3 IP mg kg-1 min-1, p < 0.01) and glucose utilization lower (4.4 +/- 1.0 IV vs 3.3 +/- 0.2 IP mg kg-1 min-1, p < 0.05) with IP delivery at the end of the matched-dose clamps. Counterregulatory hormones and hypoglycaemic symptoms increased similarly in all clamps. In summary, IP insulin, when compared to IV insulin at similar delivery rates, but not at similar insulinaemia, is associated with a less negative glucose balance (glucose production-glucose utilization) during hypoglycaemia. Such a mechanism may play a role in the reduced hypoglycaemic risk seen with IP implantable pumps.