Gliclazide potentiates suppression of hepatic glucose production in non-insulin-dependent diabetic patients.

The mechanism of the hypoglycemic action of gliclazide was evaluated in 17 diet-treated non-insulin-dependent diabetes mellitus (NIDDM) patients. In study A, five patients received a 240-minute glucose infusion along with [3-3H]glucose infusion. In study B, seven patients received a 240-minute isoglycemic insulin clamp along with [3-3H]glucose infusion. And in study C, five patients received a somatostatin infusion with basal replacing doses of insulin and glucagon. The three studies (A, B, and C) were repeated twice. Gliclazide (240 mg orally) was administered on one occasion, and placebo was given on the second occasion. Basal hepatic glucose production (HGP) and utilization and plasma glucose, insulin, C-peptide, glucagon, and free fatty acid (FFA) concentrations were similar before administration of gliclazide and placebo. In study A, plasma glucose, its incremental area, and HGP were reduced by gliclazide administration (all P < .05), but glucose utilization was not significantly affected. The increase in plasma insulin and C-peptide concentrations was similar with gliclazide and placebo, although the plasma insulin to glucose ratio was increased with gliclazide. HGP decremental area was correlated with the reduction in plasma glucose incremental area (r = -.63, P < .05). In study B, gliclazide administration produced a larger suppression of HGP, but the overall rate of glucose utilization was not different in the two studies. In study C, plasma glucose concentration and HGP progressively decreased in both studies, without a difference between gliclazide and placebo. These results suggest that under conditions of hyperglycemia and hyperinsulinemia gliclazide elicits a larger suppression of HGP.

Retrospective analysis of daily glucose profile in type 1 diabetic patients with continuous subcutaneous insulin infusion (CSII).

A retrospective analysis of blood glucose control was performed in 17 type 1 diabetic patients who regularly monitored their blood glucose concentration by visual strips over a period of 3-83 months. Analysis was performed by a patient management software loaded on a personal computer. In this cohort of patients the average daily blood glucose reading was 1.6 +/- 0.3. Blood glucose readings were collected more frequently following meal ingestion (40.3%) than in the post-absorptive state (24.6%; P less than 0.05). Blood glucose concentration fluctuated from a basal level of 146 +/- 5 mg/dl to 167 +/- 4 mg/dl in the post-prandial phases with an average daily value of 156 +/- 2 mg/dl. Blood glucose values below 80 mg/dl were evenly distributed throughout the day, while hyperglycemia (greater than 300 mg/dl) occurred more commonly after meals (42%). Daily blood glucose was higher during weekends (164 +/- 5 mg/dl) than during weekdays (155 +/- 2 mg/dl; P less than 0.05). A weak correlation was found between the number of blood glucose readings/day and daily blood glucose level. These results suggest that long-term maintenance of satisfactory metabolic control is attainable in type 1 diabetic patients and that this is mainly dependent upon subject self awareness.

[Group educational intervention in diabetic foot: the objectives, pedagogical strategies, level of knowledge and results]. / Intervento educativo di gruppo sul piede diabetico: obiettivi, strategie pedagogiche, contenuti di conoscenza, risultati.

Detailed contents and aims of an educational intervention for diabetic foot are presented, together with evaluation tools and results at 3, 6 and 12 month interval after the course. Knowledge level and "health" of the foot were assessed at 12 month interval on 2/3 of the 100 diabetic patients originally exposed to the educational intervention. After 12 months 80% of patients showed a good retention of knowledge on practical issues related to foot care, while 77% of patients with persistent foot problems were not independent (because of hypo-mobility or sight problems) in foot care.

The contribution of hyperglycaemia and hypoinsulinaemia to the insulin resistance of streptozotocin-diabetic rats.

The relative contribution of hyperglycaemia and hypoinsulinaemia was evaluated in rats made diabetic by streptozotocin administration. Four groups of rats were studied: untreated normal rats; streptozotocin-diabetic; streptozotocin-diabetic treated with phlorizin (0.4 mg/kg body weight per day); streptozotocin-diabetic mildly treated with insulin (0.7 IU/day). In all groups, insulin action (responsiveness) was assessed with the euglycaemic (5.3 mmol/l) hyperinsulinaemic (524 mU/l) clamp technique combined with 3H-2-deoxy-D-glucose method, enabling determination of the glucose utilization index in various tissues. Responsiveness of the overall glucose utilization process to insulin was reduced by 28% in streptozotocin-diabetic rats (12.0 +/- 1.2 vs 16.5 +/- 0.6 mg.kg-1.min-1, p less than 0.001). This was associated with a significant reduction (p less than 0.05) in the glucose utilization index in all muscles studied (average = 17.0 vs 32.1 ng.mg of tissue-1.min-1), in the heart (19.6 vs 39.5 ng.mg-1.min-1), brown adipose tissue (98.9 vs 178.0 ng.mg-1.min-1), skin (6.4 vs 13.1 ng.mg-1.min-1). Phlorizin treatment normalized plasma glucose levels without affecting those of insulin, and restored overall glucose utilization to normal (16.6 +/- 1.0 mg.kg-1.min-1). This normalization was accompanied by a normalization of the glucose utilization index in all muscle types studied (29.2 ng.mg-1.min-1), in the heart (50.0 ng.mg-1.min-1), brown adipose tissue (157.2 ng.mg-1.min-1), and skin (10.0 ng.mg-1.min-1). White adipose tissue, brain and gut were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Partial recovery of insulin secretion and action after combined insulin-sulfonylurea treatment in type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral agents.

Metabolic control, insulin secretion and insulin action were evaluated in seven Type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral antidiabetic agents before and after two months of combined therapy with supper-time insulin (Ultratard: 0.4 U/kg body weight/day) plus premeal glibenclamide (15 mg/day). Metabolic control was assessed by 24 h plasma glucose, NEFA, and substrate (lactate, alanine, glycerol, ketone bodies) profile. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, hyperglycaemic clamp (+ 7 mmol/l) and 24 h free-insulin and C-peptide profiles. The repeat studies, after two months of combined therapy, were performed at least 72 h after supper-time insulin withdrawal. Combining insulin and sulfonylurea agents resulted in a reduction in fasting plasma glucose (12.9 +/- 7 vs 10.4 +/- 1.2 mmol/l; p less than 0.05) and hepatic glucose production (13.9 +/- 1.1 vs 11.1 +/- 1.1 mumol.kg-1.min-1; p less than 0.05). Mean 24 h plasma glucose was also lower (13.7 +/- 1.2 vs 11.1 +/- 1.4 mmol/l; p less than 0.05). Decrements in fasting plasma glucose and mean 24 h profile were correlated (r = 0.90; p less than 0.01). HbA1c also improved (11.8 +/- 0.8 vs 8.9 +/- 0.5%; p less than 0.05). Twenty-four hour profile for NEFA, glycerol, and ketone bodies was lower after treatment, while no difference occurred in the blood lactate and alanine profile. Insulin secretion in response to glucagon (C-peptide = +0.53 +/- 0.07 vs +0.43 +/- 0.07 pmol/ml) and hyperglycaemia (freeinsulin = 13.1 +/- 2.0 vs 12.3 +/- 2.2 mU/l) did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin regulation of glucose and lipid metabolism in massive obesity.

Eight obese patients and 12 normal individuals underwent a euglycaemic insulin clamp (20 and 40 mU m2-1.min-1) along with continuous infusion of 3-3H-glucose and 1-14C-palmitate and indirect calorimetry. Basal plasma glucose concentration (4.7 +/- 0.3 vs 4.4 +/- 0.2 mmol/l) was similar in the two groups, whereas hepatic glucose production was slightly higher in obese individuals (1.11 +/- 0.06 vs 0.84 +/- 0.05 mmol/min) in spite of higher plasma insulin levels (17 +/- 2 vs 6 +/- 1 mU/l; p less than 0.01). Insulin inhibition of hepatic glucose production was impaired in obese subjects. Glucose disposal by lean body mass was markedly reduced both at baseline (11.7 +/- 1.1 vs 15.6 +/- 0.6 mumol.kg-1.min-1; p less than 0.05) and during clamp (15.0 +/- 1.1 vs 34.4 +/- 2.8 and 26.7 +/- 3.9 vs 62.2 +/- 2.8 mumol.kg-1.min-1; p less than 0.01) Oxidative (12.2 +/- 1.1 vs 17.8 +/- 1 and 16.1 +/- 1.1 vs 51.1 +/- 1.7 mumol.kg-1.min-1; p less than 0.05-0.002) and non-oxidative glucose metabolism (3.9 +/- 1.1 vs 15.0 +/- 2.8 and 12.8 +/- 3.3 vs 38.2 +/- 2.2 mumol.kg-1.min-1; p less than 0.01-0.001) were impaired. Basal plasma concentrations of non-esterified fatty acids (635 +/- 75 vs 510 +/- 71 mumol/l) and blood glycerol (129 +/- 17 vs 56 +/- 5 mumol/l; p less than 0.01) were increased in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose turnover and recycling in diabetes secondary to total pancreatectomy: effect of glucagon infusion.

This study was designed to evaluate whether chronic deficiency of pancreatic glucagon in patients with diabetes secondary to total pancreatectomy (PX) is responsible for the commonly observed increase in blood concentrations of gluconeogenic precursors (alanine, lactate, and pyruvate). Seven PX patients were studied on two different occasions: 1) after an overnight insulin infusion (0.15 mU/kg.min) and 2) after an overnight insulin/glucagon infusion (2 ng/kg.min). Five type 1 diabetic individuals were also studied after a similar overnight insulin infusion. In the morning of each study day, [6-3H]glucose and [1-14C]glucose were rapidly injected for determination of total glucose turnover rate [( 6-3H]glucose) and glucose recycling (difference between [6-3H]glucose and [1-14C]glucose turnover rate). Basal concentrations of hormones, glucose, and intermediary metabolites were measured. After overnight insulin infusion, plasma glucose concentration (3.8 +/- 0.4 vs. 6.8 +/- 1.4 mmol/L), turnover rate (8.4 +/- 1.0 vs. 13.7 +/- 1.9 mumol/kg.min), and percent glucose recycling (5.6 +/- 3.9% vs. 19.0 +/- 3.8%) were significantly lower in PX patients than in type 1 diabetic individuals (P less than 0.05-0.01). On the contrary, blood alanine (459 +/- 93 vs. 263 +/- 28 mumol/L), lactate (1157 +/- 109 vs. 818 +/- 116 mumol/L), and pyruvate (71 +/- 8 vs. 42 +/- 3 mumol/L) were significantly higher than those values in type 1 diabetic patients (P less than 0.05-0.01). Insulin/glucagon infusion increased plasma glucose concentration (8.7 +/- 1.5 mmol/L), total turnover (18.1 +/- 1.7 mumol/kg.min), and percent recycling (20.4 +/- 6.6%) to values similar to those in type 1 diabetic subjects. The change in glucose metabolism was associated with a significant drop in blood concentrations of alanine (179 +/- 24 mumol/L), lactate (611 +/- 25 mumol/L), and pyruvate (30 +/- 3 mumol/L; all P less than 0.05-0.01 vs. insulin infusion alone). In PX patients, the glucose turnover rate was inversely correlated with blood concentrations of both alanine (r = 0.67) and lactate (r = 0.71; P less than 0.01). In conclusion, chronic deficiency of pancreatic glucagon in PX patients 1) is associated with a decreased rate of glucose turnover, 2) causes a marked impairment in glucose recycling (an index of the activity of hepatic gluconeogenesis), and 3) increases blood concentrations of alanine, lactate, and pyruvate. All abnormalities are reversed by glucagon.

'Do-it-yourself' insulin pump. Case report.

We report the case of a highly motivated diabetic patient who designed and developed an insulin injector for himself. During 4 years of use of this injector, a strict control was achieved and the frequency of hypoglycemic episodes was reduced. During this period there was no evidence of progression of diabetic complications.

Metabolic control during total parenteral nutrition: use of an artificial endocrine pancreas.

The metabolic impact of total parenteral nutrition (TPN) was evaluated in nine subjects who underwent esophagogastroplasty for esophageal carcinoma. On the second day after operation all subjects were connected to an artificial endocrine pancreas. In four patients only glucose was infused (5.5 mg/kg X min). The remaining five subjects received glucose (4.0 mg/kg X min), amino acid (0.5 mg/kg X min), and lipid emulsion (0.6 mg/kg X min). Plasma glucose concentration was kept constant over 24 hours. However, both insulin requirement (111 +/- 15 v 70 +/- 2 mU/kg X h) and plasma insulin level (99 +/- 15 v 30 +/- 7 microU/mL; P less than .01) were higher during combined TPN. Blood lactate concentration was higher during glucose infusion (P less than .05). No difference was found in blood concentrations of pyruvate, alanine, and ketone bodies. Both glycerol and FFA were higher during combined TPN. The ratio between glucose infusion rate and the average plasma insulin level was calculated as an index of insulin-mediated glucose metabolism; G/I X 100 was markedly reduced during combined TPN (4.5 +/- 0.8 v 20.7 +/- 3.7; P less than .05). Plasma FFA levels were positively correlated with plasma insulin concentration (r = .76) and inversely correlated to G/I X 100 (r = -.73; both P less than .05). In conclusion, during combined TPN a state of insulin resistance is induced and more insulin is required to achieve a normal glucose utilization.