Gastric and oesophageal emptying in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects. In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined. The percentage of the solid meal remaining in the stomach at 100 min (p<0.001), the 50% gastric emptying time for the liquid meal (p<0.05) and oesophageal emptying (p<0.05) were slower in the diabetic patients compared to the control subjects. Scores for upper gastrointestinal symptoms and autonomic nerve dysfunction did not correlate significantly (p>0.05) with oesophageal, or gastric emptying. The 50% gastric emptying time for the liquid meal was positively related (r=0.58, p<0.01) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p<0.05) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median. These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations.     

Gastric and oesophageal emptying in insulin-dependent diabetes mellitus

Abstract Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 45 randomly selected insulin-dependent diabetics and in 22 control subjects. In the diabetics, the relationships between oesophageal emptying, gastric emptying, age, duration of diabetes mellitus, upper gastrointestinal symptoms, glycaemic control and the complications, autonomic neuropathy, peripheral neuropathy and retinopathy were examined. The lag period before solid food left the stomach was not significantly different in diabetics compared with control subjects, but the percentage retention of solid food at 100 min was greater ( P < 0.001) in the diabetic subjects. Both the early phase (percentage retention at 10 min) and the 50% emptying time for liquid gastric emptying were delayed ( P < 0.001) in the diabetic subjects. Of the diabetics, 58% had delayed gastric emptying of either the solid and/or the liquid meal; oesophageal emptying was delayed in 42%. Upper gastrointestinal symptoms correlated poorly with both gastric and oesophageal emptying. Oesophageal emptying, solid gastric emptying and the liquid 50% emptying time correlated with the severity of autonomic nerve dysfunction ( P < 0.05). The early phase of liquid emptying (retention at 10 min) was significantly slower ( P < 0.05) in patients with mean plasma glucose concentrations of > 15 mmol/l during the gastric emptying test and the lag period for solid emptying correlated with both the glycosylated haemoglobin and mean plasma glucose concentrations.     

The influence of plasma glucose upon pulsatile ocular blood flow in subjects with Type II diabetes mellitus

Abstract Aims/hypothesis. This study investigated the influence of plasma glucose upon pulsatile ocular blood flow in subjects with Type II (non-insulin-dependent) diabetes mellitus. Methods. A total of 19 subjects with Type II diabetes and 8 normal control subjects undertook a meal tolerance test after an overnight fast. The pulsatile ocular blood flow, using the Ocular Blood Flow Tonometer, and plasma glucose concentrations were taken at times 0 min, 90 min and 240 min. Blood pressure and glycated haemoglobin concentrations, in the subjects with diabetes, were also measured at time 0 min. Pulsatile ocular blood flow and plasma glucose were also measured at times 0 and 90 min in 5 subjects with Type II diabetes mellitus who remained fasting. Results. It was found that the subjects with diabetes who undertook the meal tolerance test showed a significant increase in both plasma glucose concentrations and pulsatile ocular blood flow from time 0–90 min, followed by a decrease from 90 min to the end of the session at 240 min. (p < 0.001 in each case). Regression analysis showed a significant correlation between the change in pulsatile ocular blood flow and the change in plasma glucose concentration (r = 0.671, p = 0.001). Control subjects showed no significant change in either plasma glucose or pulsatile ocular blood flow during the meal tolerance test. Subjects with diabetes mellitus who remained fasting also showed no significant change in pulsatile ocular blood flow or plasma glucose concentrations. No correlation was found between glycated haemoglobin concentrations or blood pressure and pulsatile ocular blood flow. Conclusion/interpretation. Pulsatile ocular blood flow is influenced by changes in plasma glucose concentrations in Type II diabetes mellitus, indicating that uncontrolled hyperglycaemia might result in a higher pulsatile ocular blood flow than might otherwise be expected. [Diabetologia (2001) 44: 700–705] Received: 7 November 2000 and in revised form: 6 February 2001     

Production and metabolic clearance of glucose under basal conditions in Type II (non-insulin-dependent) diabetes mellitus

Aims/hypothesis: The pathogenesis of fasting hyperglycaemia in Type II (non-insulin-dependent) diabetes mellitus has yet to be clarified. Rates of glucose production (R _a), utilization and metabolic clearance rate were therefore measured during an extended fast, in control subjects and in Type II diabetic patients. Methods: Nine subjects with newly-diagnosed or diet-treated diabetes and seven control subjects matched for age and weight (BMI 36.0 ± 2.4 and 35.3 ± 3.1 kg/m² respectively) underwent an overnight fast followed by a 10-h unprimed infusion of [6-³H]glucose. Plasma tracer concentrations were fitted by a single-compartment model. Results: The metabolic clearance rate was near-constant [61.7 + 2.4 ml/(min-m²)] in diabetic patients and [75.5 ± 3.3 ml/(min-m²)] in control subjects (p < 0.05). It was correlated to the glucose concentrations both at t = 0 (r = –0.752, p = 0.0008) and t = 10 h (r = –0.675, p = 0.004). The calculated volume of distribution was 17.3 ± 1.4 l (18.2 % weight, diabetes), 19.6 ± 2.4 l (18.4 % weight, control). Glycaemia fell from 10.7 ± 0.8 mmol/l to 6.5 ± 0.3 mmol/l by 10 h (p < 0.05) in diabetes and from 5.6 ± 0.6 to 4.8 ± 0.1 mmol/l in control subjects (p < 0.05). The rate of glucose production decreased in parallel, from 563 ± 33 to 363 ± 23 μmol/(min-m²) (p < 0.05) in diabetes from 419 ± 20 to 347 ± 32 μmol/(min-m²) in control subjects. Initial R _a was higher in diabetic patients than in control subjects (p < 0.05) and was highly correlated to glycaemia (r = 0.836, p = 0.0001). By 10 h, R _a had converged in diabetic patients and control subjects and all correlation with glycaemia was lost (r = 0.0017, p = 0.95). Conclusions/interpretation: In relatively early diabetes, the more “labile” portion of fasting hyperglycaemia, which subsequently decreased, was closely related to the simultaneously decreasing R _a. The 25 % increase in glucose concentrations which persisted as stabilized R _a, resulted from about a 20 % lower metabolic clearance rate. [Diabetologia (2001) 44: 983–991] Received: 28 February 2001 and in revised form: 17 April 2001     

Rapid gastric emptying of a liquid meal in long-term Type 2 diabetes mellitus

Both delayed and accelerated gastric emptying rate (GER) have been reported in patients with diabetes mellitus. Delayed GER has been attributed to autonomic neuropathy in established diabetes but rapid GER was demonstrated in early Type 2 diabetes. The aim of the study was to investigate rapid gastric emptying in a group of people with long-duration Type 2 diabetes. GER of a radiolabelled liquid meal was studied scintigraphically in 20 Type 2 patients with a mean (± SEM) duration of diabetes 13 (±1) years. The 50 % emptying time (t₅₀) for the liquid meal was shorter in diabetic patients (29.6 ± 2.1 min) than in controls (39.2 ± 1.9 min; p<0.0005). Accelerated emptying (t₅₀ value below the shortest t₅₀ of controls) was evidenced in 14/ 20 patients and delayed emptying (t₅₀ value exceeding the upper t₅₀ of controls) in none. Patients with accelerated GER were comparable for BMI, diabetes duration, HbA_1c and fasting glycaemia to those with normal GER. Rapid GER for liquids was found in the presence or absence of autonomic neuropathy. Seven of the patients with rapid emptying of the liquid meal were reassessed using a solid meal. Only one patient demonstrated rapid emptying of the solid meal, which was normal in 3 and delayed in 3 patients. In conclusion, accelerated GER can be found in long-term Type 2 diabetes but there is no concordance between GER of a liquid and a solid meal. Copyright © 1998 John Wiley & Sons, Ltd.     

Euglycaemic hyperinsulinaemia does not affect gastric emptying in Type I and Type II diabetes mellitus

Summary Hyperglycaemia slows gastric emptying in both normal subjects and patients with diabetes mellitus. The mechanisms mediating this effect, particularly the potential role of insulin, are uncertain. Hyperinsulinaemia has been reported to slow gastric emptying in normal subjects during euglycaemia. The purpose of this study was to evaluate the effect of euglycaemic hyperinsulinaemia on gastric emptying in Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus. In six patients with uncomplicated Type I and eight patients with uncomplicated Type II diabetes mellitus, measurements of gastric emptying were done on 2 separate days. No patients had gastrointestinal symptoms or cardiovascular autonomic neuropathy. The insulin infusion rate was 40 mU · m^–2· min^–1 on one day and 80 mU · m^–2· min^–1 on the other. Gastric emptying and intragastric meal distribution were measured using a scintigraphic technique for 3 h after ingestion of a mixed solid/liquid meal and results compared with a range established in normal volunteers. In both Type I and Type II patients the serum insulin concentration had no effect on gastric emptying or intragastric meal distribution of solids or liquids. When gastric emptying during insulin infusion rates of 40 mU · m^–2· min^–1 and 80 mU · m^–2· min^–1 were compared the solid T₅₀ was 137.8 ± 24.6 min vs 128.7 ± 24.3 min and liquid T₅₀ was 36.7 ± 19.4 min vs 40.4 ± 15.7 min in the Type I patients; the solid T₅₀ was 94.9 ± 19.1 vs 86.1 ± 10.7 min and liquid T₅₀ was 21.8 ± 6.9 min vs 21.8 ± 5.9 min in the Type II patients. We conclude that hyperinsulinaemia during euglycaemia has no notable effect on gastric emptying in patients with uncomplicated Type I and Type II diabetes; any effect of insulin on gastric emptying in patients with diabetes is likely to be minimal. [Diabetologia (1999) 42: 365–372] Received: 3 September 1998 and in revised form: 3 November 1998     

Occurrence of low blood glucose concentrations during the afternoon in Type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring

Summary The European NIDDM Policy Group states that the lowest target for good control of Type 2 (non-insulin-dependent) diabetic patients is a blood glucose level 4.4 mmol/l, both fasting and postprandially. The aim of this study is to evaluate the occurrence and temporal distribution of values under this target in the clinical records of 463 Type 2 diabetic patients, treated by diet or diet and oral hypoglycaemic agents, monitored for at least 2 years. The protocol includes blood glucose measurements after overnight fasting (08.00 hours), 120–150 min after breakfast (11.00 hours) and 120 and 240 min after lunch (14.00 and 16.00 hours). At least one blood glucose concentration of less than 4.4 mmol/l was presented by 42% of the patients. The only difference between patients showing and not showing glycaemic levels under this target was the higher percentage on oral hypoglycaemic agents in the first group (68.4% vs 56.9%, p=0.016). We considered 299 blood glucose profiles containing at least one value of less than 4.4 mmol/l, observing that a) 46.9% of profiles from patients treated by diet alone and 68.7% of profiles from patients treated both by diet and oral hypoglycaemic agents presented the lowest blood glucose concentration at 16.00 hours (p=0.002). b) No correlation existed between fasting blood glucose and values at 16.00 hours in profiles from diet-treated patients, whereas a negative correlation was present in patients on diet and oral hypoglycaemic agents, indicating that an excess of oral agents, administered to correct fasting hyperglycaemia. was the cause of the low glycaemic values in the afternoon. c) 37.9% of profiles on a diet and 83.3% of profiles on diet and oral agents showed fasting glucose concentrations >6.7 mmol/l, the upper limit of good control according to the European NIDDM Policy Group. This indicates that fasting hyperglycaemia does not exclude the occurrence of low glucose values throughout the day and that it is necessary to monitor blood glucose profiles.     

Relationship between blood glucose level and mortality in Type 2 diabetes mellitus: a systematic review

Aim To review the relationship between blood glucose level and mortality in patients with Type 2 diabetes mellitus (DM) as reported in the literature. Methods Literature search using Medline Search: January 1966 – April 1998. Keywords: Diabetes, Non Insulin Dependent, Mortality. Inclusion criteria for papers were: Type 2 DM; follow-up for at least 3 years; glucose or glycated haemoglobin (HbA_1c) was used as parameter; published in the form of an article. Additionally all references in the selected articles that dealt with the relationship between blood glucose level and mortality in Type 2 DM were included in the search. Results Twenty-seven eligible articles were found. Twenty-three of them showed a positive association: measures of elevated blood glucose concentrations were associated with higher mortality; in 15 out of 23 studies the positive association was statistically significant, in two only for postprandial blood glucose. One study found a nonsignificant negative relationship in a very old population. Conclusion In the literature there is a positive, but rather weak, association between the measures of blood glucose control and the risk of dying of patients with Type 2 DM. In the six larger studies (more than 100 deceased patients) that used a continuous categorization of glycaemia, the Risk ratio per unit varies from 1.03 to 1.12. Diabet. Med. 16, 2–13 (1999)     

Hyperglycaemia slows gastric emptying in Type 1 (insulin-dependent) diabetes mellitus

Summary In 10 patients with Type 1 (insulin-dependent) diabetes mellitus gastric emptying of a digestible solid and liquid meal was measured during euglycaemia (blood glucose concentration 4–8 mmol/l) and during hyperglycaemia (blood glucose concentration 16–20 mmol/l). Gastric emptying was studied with a scintigraphic technique and blood glucose concentrations were stabilised using a modified glucose clamp. Patients were also evaluated for gastrointestinal symptoms, autonomic nerve function and glycaemic control. When compared to euglycaemia, the duration of the lag phase before any of the solid meal emptied from the stomach (p = 0.032), the percentage of the solid meal remaining in the stomach at 100 min (p = 0.032) and the 50% emptying time for the solid meal (p = 0.032) increased during hyperglycaemia. The 50% emptying time for the liquid meal (p = 0.042) was also prolonged during the period of hyperglycaemia. These results demonstrate that the rate of gastric emptying in Type 1 diabetes is affected by the blood glucose concentration.     

Gastrointestinal motor function in diabetes mellitus: Relationship to blood glucose concentrations

Abstract The application of novel investigative techniques has established that there is a high prevalence of disordered gastrointestinal motor function in patients with diabetes mellitus and has provided insights into its pathogenesis and clinical significance. Acute changes in the blood glucose concentration, even within the normal postprandial range, affect both gastrointestinal motor function and the perception of sensations arising from the gastrointestinal tract. Gastric emptying is slower during hyperglycaemia and accelerated during hypoglycaemia; the perception of gastric distension is greater during hyperglycaemia than euglycaemia. The pathways mediating the effects of the blood glucose concentration on gut motility and sensation are poorly defined. The rate of gastric emptying is an important determinant of postprandial blood glucose concentrations and there is increasing evidence that gastric emptying can be modulated therapeutically in order to optimize glycaemic control in patients with diabetes.     

The effect of acute hyperglycaemia on appetite and food intake in Type 1 diabetes mellitus.

AIMS: To determine the effects of acute hyperglycaemia on appetite and food intake in Type 1 diabetes mellitus. METHODS: Two separate studies, each involving eight adults with uncomplicated Type 1 diabetes, were performed: one in the fasted state (A) and the other after a nutrient preload (B). In both studies, perceptions of appetite (hunger and fullness) and food intake at a buffet meal were evaluated during euglycaemia (blood glucose, approximately 6 mmol/l) and hyperglycaemia (blood glucose, approximately 14 mmol/l). Both experiments were randomized and single-blind. In study A, appetite was assessed in the fasted state for 90 min before the buffet meal. In study B, a nutrient 'preload' of Ensure and milk containing 13C-octanoic acid was consumed 90 min before the meal. Gastric emptying of the preload was quantified with a radioisotopic breath test technique. RESULTS: There was no significant difference in plasma insulin concentrations between euglycaemia and hyperglycaemia in either study. In study A, there were no differences in hunger, fullness or energy intake between the two treatment days. In study B, subjects were slightly less hungry between the preload and buffet meal during hyperglycaemia than euglycaemia (P = 0.04), and tended to have slower gastric emptying during hyperglycaemia (emptying coefficient, 3.89 +/- 0.16 vs. 3.57 +/- 0.21; P = 0.052), but there was no difference in food intake between hyperglycaemia and euglycaemia. CONCLUSIONS: Acute hyperglycaemia suppresses hunger after a nutrient preload, but not in the fasted state, in patients with uncomplicated Type 1 diabetes. This effect is small and not associated with changes in food intake.     

The blood glucose lowering effects of exercise and glibenclamide in patients with Type 2 diabetes mellitus

Physical exercise is associated with a fall in serum insulin levels, whereas sulphonylurea administration increases insulin release. To date, the opposing effects of exercise and sulphonylurea administration have not been systematically studied in Type 2 diabetic patients, who are not infrequently treated with sulphonylureas. In this study nine patients with Type 2 diabetes mellitus were subjected to four treatments in random order on separate days: (A) endurance exercise after the administration of 3.5 mg glibenclamide; (B) as A but given only 1.75 mg glibenclamide; (C) as A but with placebo; (D) rest and administration of 1.75 mg glibenclamide. Exercise and placebo resulted in only a small decrease in glycaemia. Rest and administration of 1.75 mg glibenclamide led to a moderate but steady fall in blood glucose concentrations. If glibenclamide administration and exercise were combined, blood glucose concentrations declined more markedly. Serum insulin concentrations showed a physiological decrease during exercise and placebo administration. If patients rested after administration of glibenclamide serum insulin levels rose and remained elevated. When exercise and glibenclamide were combined the rise in serum insulin levels was blunted and insulin levels fell once exercise was begun. Thus, exercise attenuates the glibenclamide induced increase in serum insulin in moderately hyperglycaemic Type 2 diabetic patients. Nevertheless, exercise has a substantial hypoglycaemic effect in glibenclamide treated Type 2 diabetic patients. © 1998 John Wiley & Sons, Ltd.     

Hyperglycaemic symptoms before diagnosis of non-insulin-dependent (type 2) diabetes mellitus in relation to 5-year outcome.

A group of newly diagnosed patients with non-insulin-dependent (type 2) diabetes mellitus (n = 133) were divided into two groups according to the symptoms of diabetes mellitus at diagnosis; a group (26 men and 17 women) with hyperglycaemic symptoms (polydipsia, polyuria, weight loss and tiredness) and a group (44 men and 46 women) without such symptoms. At the time of diagnosis, symptomatic patients tended to be leaner (P = NS), and they were more hyperglycaemic (P less than 0.001-0.06) and had lower insulin responses to an oral glucose load (P less than 0.01-0.05) than asymptomatic patients, but after 5 years no difference in these respects was found. No significant differences in the frequency of islet-cell antibodies or cardiovascular diseases were found between the two diabetic groups. At the 5-year examination, the initially symptomatic patients were receiving pharmacological treatment for hyperglycaemia more often than asymptomatic patients. No consistent differences in clinical characteristics and 5-year outcome were observed between those diabetic patients who were diagnosed on the basis of hyperglycaemic symptoms and those who were diagnosed for other reasons. In conclusion, in middle-aged patients with newly diagnosed diabetes mellitus classified as non-insulin-dependent, diabetic symptoms at diagnosis did not predict the 5-year outcome of the patients in terms of metabolic control or cardiovascular events.     

Albuminuria in Type 2 (non-insulin-dependent) diabetes mellitus and impaired glucose tolerance in Pima Indians

Summary The prevalence of abnormal urinary albumin excretion, defined by a urine albumin to creatinine ratio>-30 mg/g (approximately equivalent to an albumin excretion rate of >-30 mg/24 h), was determined in 2728 Pima Indians aged >-15 years from the Gila River Indian Community in Arizona, a population with a high prevalence of Type 2 (non-insulin-dependent) diabetes mellitus. Excessive albumin excretion was present in 8% of subjects with normal glucose tolerance, 15% of those with impaired glucose tolerance, and 47% of subjects with diabetes. The intermediate prevalence of abnormal albuminuria in those with impaired glucose tolerance suggests that hyperglycaemia even at levels below those diagnostic of diabetes is associated with renal abnormalities in some subjects and that these abnormalities may precede the onset of diabetes. Abnormal albuminuria at levels not reliably detected by the usual dipstick methods was commonly observed in Pima Indians with diabetes, even those with diabetes of recent onset. Associations were found with age, duration of diabetes, level of glycaemia, blood pressure, and treatment with insulin.     

Treatment of patients with non-insulin-dependent diabetes mellitus: diabetic control and insulin secretion and action after different treatment modalities

In order to define the relationship between treatment-induced changes in diabetic control and improvement in in vivo insulin-stimulated glucose utilization (insulin clamp technique) 30 patients with non-insulin-dependent diabetes mellitus (NIDDM) were treated with either insulin, glipizide or diet alone, depending on their initial weight. Fasting plasma glucose concentrations fell from 16.3 +/- 1.2, 15.9 +/- 1.0, and 16.3 +/- 1.0 mmol/l, (mean +/- SE) to 6.3 +/- 0.5, 11.6 +/- 0.6, and 13.4 +/- 1.6 mmol/l, after insulin, glipizide and weight reduction, respectively. These changes in fasting plasma glucose concentration were associated with an improvement in insulin-stimulated glucose uptake, which increased by 69% after insulin, 45% after glipizide, and 72% after weight reduction. Thus, the improvement in insulin action was comparable in the three different groups of patients following each therapeutic intervention, and appeared to be unrelated to the fall in plasma glucose concentration. These results appear to suggest that the ability of any specific treatment to improve diabetic control can vary independently of its effect on in vivo insulin-stimulated glucose utilization.     

Serum proinsulin levels at fasting and after oral glucose load in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary A simple and sensitive human proinsulin radioimmunoassay system was developed using guinea pig antiproinsulin serum, which cross-reacted neither with human insulin nor C-peptide. The recognition site of the antiserum seems to be located near the junction between the B chain and C-peptide. With this assay system, we studied the serum proinsulin concentration at fasting and after an oral 100 g glucose load in 25 healthy subjects, 21 subjects with impaired glucose tolerance and 40 patients with Type 2 (non-insulin-dependent) diabetes mellitus. At fasting, serum proinsulin was 5.8±3.3 pmol/l in normal subjects as compared to 9.5±6.9 pmol/l (p<0.05) in subjects with impaired glucose tolerance and 12.6±7.5 pmol/l (p<0.001) in diabetic patients. The molar ratio of proinsulin to insulin was also increased in subjects with impaired glucose tolerance or diabetes compared to control subjects. After a 100 g oral glucose load, serum proinsulin increased more slowly than insulin. The proinsulin response after an oral glucose load was augmented in subjects with impaired glucose tolerance and diabetes, while the insulin response decreased with the elevation of fasting plasma glucose. Diabetic patients with high fasting plasma glucose had a very poor insulin response, but the proinsulin response was similar to control subjects. There was a linear correlation between summed proinsulin values and summed insulin values, but the slope of the regression line was steeper in diabetic patients than in control subjects. There was a relative increase in serum proinsulin both in subjects with impaired glucose tolerance and diabetic patients. We suggest that B cells may release ‘immature’ granules richer in proinsulin content as well as mature granules in the over-stimulated state.     

Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Proteins and lipids are among the prime targets for oxidative stress. In the present study, the oxidative stress was evaluated in 55 diabetic patients and 40 healthy subjects by measuring the levels of protein oxidation, lipid peroxidation and some enzymatic and nonenzymatic antioxidants. The oxidative products of protein (PCG) and lipid peroxidation (MDA) and nitric oxide levels in plasma of NIDDM patients were significantly increased. However, the levels of enzymatic (GPx, SOD, catalase in RBC) and nonenzymatic (β-carotene, retinol, vitamin C & E and uric acid) antioxidants of RBC showed a significant decrease in NIDDM patients compared to normal subjects. Serum protein analysis by polyacrylamide gel electrophoresis (PAGE) showed the significant difference in the ceruloplasmin, transferrin, albumin, retinal binding protein, etc. in diabetic patients compared to healthy controls. In conclusion, the results suggest that increased protein oxidation, lipid peroxidation and NO levels, decreases the levels of enzymatic and nonenzymatic antioxidants and playing a major role in diabetic complications.     

Effect of hyperglycaemia on gallbladder motility in Type 1 (insulin-dependent) diabetes mellitus

Summary Patients with diabetes mellitus are at increased risk of developing gallstones. This has been attributed, among other factors, to alterations in gallbladder motility in the presence of autonomic neuropathy. Since high blood glucose concentrations impair gastric emptying in diabetic patients, we have investigated the effect of acute hyperglycaemia on gallbladder motility. Seven Type 1 (insulin-dependent) diabetic patients were studied twice during euglycaemia (blood glucose 5 mmol/l) and hyperglycaemia (blood glucose 15 mmol/l) using a clamp technique. In addition, seven healthy volunteers were studied during euglycaemia and hyperglycaemia. Gallbladder volumes, measured with ultrasonography, were studied before and during infusion of step-wise increasing doses of cholecystokinin-33, 0.25, 0.5 and 1.0 Ivy Dog Unit · kg^–1 · h^–1, each dose for 30 min. Mean basal gallbladder volumes were not significantly different in the four experiments. Administration of cholecystokinin resulted in significant (p<0.05) dose-dependent reductions in gallbladder volume in all experiments. During euglycaemia the gallbladder contraction in diabetic patients was not significantly different from the control subjects. During hyperglycaemia the gallbladder contraction in the diabetic patients was significantly (p<0.05) reduced compared to euglycaemia only during infusion of 0.25 Ivy Dog Unit · kg^–1 · h^–1 of cholecystokinin (19±6% vs 33±6%). Compared to euglycaemia, during hyperglycaemia the gallbladder contraction in the control subjects was significantly (p<0.05) reduced during infusion of 0.25, 0.5 and 1.0 Ivy Dog Unit · kg^–1 · h^–1 of cholecystokinin (14±4% vs 31±3%; 42±6% vs 65±5%; 74±4% vs 90±3%, respectively). It is concluded that during euglycaemia the gallbladder contraction in response to cholecystokinin in Type 1 diabetic patients is not significantly different from control subjects. During hyperglycaemia the gallbladder contraction in response to 0.25 Ivy Dog Unit · kg^–1 · h^–1 cholecystokinin, leading to cholecystokinin levels as observed after ingestion of a light meal, is significantly reduced in Type 1 diabetic patients.     

Insulin action and determinants of glycaemia in a rat model of Type 2 (non-insulin-dependent) diabetes mellitus

Summary We aimed to assess prandial responses, basal glucose turnover and insulin action (euglycaemic clamp) in a very low-dose neonatal streptozotocin model of Type 2 (noninsulin-dependent) diabetes mellitus. Male Wistar rats were injected at 2 days of age with 45 mg/kg streptozotocin or vehicle (control). At 8 weeks, the groups were subdivided and fed either a high-fat or high-starch diet for 3 weeks. Both the fat diet and streptozotocin treatments had independent hyperglycaemic effects (streptozotocin/fat 9.3±0.3 mmol/l; streptozotocin/starch 7.5±0.3 mmol/l; control/fat 7.4±0.1 mmol/l; all p<0.01 vs control/starch 6.4±0.1 mmol/l). The fat diet effect was associated with both a reduction in basal glucose clearance (p<0.001) and in basal hepatic glucose output (p<0.05). Streptozotocin increased basal hepatic glucose output. Significantly higher prandial glycaemia in the streptozotocin/starch group occurred despite similar insulin levels and appeared to be related to an impaired early insulin response. Whole-body and tissue-specific insulin sensitivity were significantly depressed in fat-fed animals compared to starch-fed animals, however there were no significant effects of streptozotocin treatment. We conclude that fasting hyperglycaemia associated with abnormalities in both glucose production and clearance can exist in the presence of a basal hepatic glucose output which is reduced compared to control animals. Furthermore, dietary-fat-induced insulin resistance is not exacerbated by the relative insulin deficiency and/or mild hyper glycaemia observed when dietary fat and neonatal streptozotocin-treatments are combined.     

Considerations on blood glucose management in Type 2 diabetes mellitus

In recent years the benefits of more intensive management in preventing or delaying the development and progression of diabetic complications have been well documented. What is not as well documented is how to motivate the person with diabetes to manage the condition, how to set, assess and quantify glucose goals, and the glucose variables that should be routinely measured. This review discusses the importance of setting targets and communicating them in a way that the patient understands. When aiming for a glycaemia target, balance is required (1) between achieving reduction of complications and causing an increased degree of hypoglycaemia, and (2) between what is achievable and what degree of benefit is gained. Target values given in guidelines should be adapted by the clinician to take into account the patient's susceptibility to hypoglycaemia, stage and type of complications, age and life expectancy, co-morbidity, social environment, understanding of the steps required and level of commitment to the treatment. Several suggestions are given regarding possible improvements and amendments to existing guidelines for diabetes management in treating to glucose goal. For example, attention should be drawn to the need to individualize goals and to consider education, long-term support, patient needs and treatment outcome when formulating diabetes management plans. The relative properties of the different glucose variables-fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated haemoglobin A(1c) (HbA(1c)), and glycated protein-in terms of their convenience of measurement, usefulness and relevance to the physician and patient are also evaluated. When prioritising the variables to be measured it is suggested that where feasible, HbA(1c) should be the standard measurement by which to gauge risk and treatment efficacy. Serial measurements should be made and, where possible, the use of blood glucose meters encouraged, in order to obtain a blood glucose profile for the patient.