Effects of different glycaemic index foods and dietary fibre intake on glycaemic control in Type 1 diabetic patients on intensive insulin therapy

To evaluate the influence of a low glycaemic index (GI), high GI and high fibre diet on glycaemic control and insulin requirement in Type 1 diabetic patients on intensive insulin therapy, nine well-controlled, highly-motivated Type 1 diabetic patients were put on a control diet for 12 days and then randomized in a consecutive manner to 12 days of each diet, in a crossover design. During each experimental diet, the study subjects adjusted their premeal insulin (soluble) dose to maintain their 1-h postprandial capillary glucose at or below 10 mmol l⁻¹. At the end of each experimental diet, they were submitted to a standardized breakfast of the diet under study, using the same premeal insulin dose as that required for the control diet. The control diet contained 16.0 ± 3.0 g of fibre day⁻¹ with a GI of 77.4 ± 2.7 compared to 15.3 ± 6.3 and 66.2 ± 1.2 for the low GI diet, 17.1 ± 7.2 and 92.9 ± 3.6 for the high GI diet, and 56.1 ± 3.6 (including 15 g of guar) and 73.5 ± 2.1 for the high fibre diet. Prebreakfast capillary blood glucose (6.2 ± 1.2 mmol l⁻¹) on the low GI diet and postbreakfast capillary blood glucose (8.7 ± 1.8 mmol l⁻¹) on the high fibre diet were significantly lower than the values obtained with the control diet (8.0 ± 1.8 and 10.6 ± 2.4, respectively; p <0.05). No change in premeal or basal insulin dose was required. During the standardized breakfasts, the incremental area under the curve was 1.6 ± 1.5 mmol l⁻¹ min⁻¹ for the control diet compared to 1.1 ± 1.8 for the low GI diet, 3.2 ± 1.4 for the high GI diet (p <0.05 versus low GI and high fibre; p = 0.08 versus control), and 1.0 ± 0.9 for the high fibre diet. These observations indicate that in well-controlled Type 1 diabetic subjects on intensive insulin therapy, major alterations in the GI and fibre content of meals induce small but significant changes in glucose profile. In everyday life, however, these differences are blunted, and plasma glucose remains within the target range for optimal metabolic control. © 1998 John Wiley & Sons, Ltd.     

Troglitazone,an insulin action enhancer,improves glycaemic control and insulin sensitivity in elderly Type 2 diabetic patients

The management of Type 2 diabetes mellitus with currently available oral agents may be complicated in the elderly by an increased frequency of side-effects. The effects of troglitazone, an insulin action enhancer, were studied in elderly patients with Type 2 diabetes in a double-blind, parallel-group, placebo-controlled trial. A total of 229 patients (41 % male), mean age 75 (range 69–85) years, with two fasting capillary blood glucose values ≥7 and ≤15 mmol l⁻¹ (and within 4.0 mmol l⁻¹ of each other) and previously treated with either diet alone (30 %) or oral hypoglycaemic agents, were randomized to placebo or troglitazone 400 mg once daily or 200 mg twice daily, or 800 mg once daily or 400 mg twice daily, for 12 weeks. After 12 weeks’ treatment, fasting serum glucose was significantly lower in troglitazone-treated patients (troglitazone, adjusted geometric mean 9.4–10.4 mmol l⁻¹ vs placebo 12.7 mmol l⁻¹, p<0.001). Adjusted geometric mean fructosamine was also lower in troglitazone-treated patients by 5 to 15 % compared to placebo (P <0.05 at all doses except 400 mg od). There was no significant difference between troglitazone doses for improvement in glycaemic control. Troglitazone lowered adjusted geometric mean fasting plasma insulin by 27–34 % compared to placebo (P<0.001) and insulin sensitivity (HOMA-S) improved by 9–15 % in all troglitazone dose groups (p<0.001). Troglitazone also lowered serum non-esterified fatty acids and triglyceride. Adverse event incidence in troglitazone-treated patients was similar to that in patients treated with placebo. No weight gain or symptomatic hypoglycaemia was recorded at any of the doses studied. Troglitazone is effective and well tolerated in elderly patients with Type 2 diabetes mellitus, providing improved glycaemic control in the absence of weight gain. © 1998 John Wiley & Sons, Ltd.     

Atrial natriuretic peptide increases urinary albumin excretion in men with Type 1 diabetes mellitus and established microalbuminuria

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l⁻¹ in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg⁻¹ plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9 % saline), low dose (2.5 pmol kg⁻¹ min⁻¹) or high dose (5.0 pmol kg⁻¹ kg min⁻¹) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) μg min⁻¹; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) μg min⁻¹, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) μg min⁻¹, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM. © 1998 John Wiley & Sons, Ltd.     

The effect of insulin infusion on capillary blood flow in the diabetic neuropathic foot.

The effect of a short-term improvement in glycaemic control induced by insulin infusion on foot skin capillary blood flow was previously unknown. In seven Type 2 (non-insulin-dependent) diabetic subjects with neuropathy capillary blood flow was measured in the great toe nailfold by television microscopy. An estimate of arteriovenous shunt flow was obtained simultaneously in the pulp of the great toe by laser Doppler flowmetry. After omission of oral hypoglycaemic therapy for 24 h mean blood glucose was 15.7 +/- 0.7 (SEM) mmol l-1. A priming infusion of 0.1 U kg-1 of insulin was given intravenously over 15 min, followed by a variable rate insulin infusion adjusted to steadily reduce blood glucose avoiding hypoglycaemia. At the end of the study blood glucose was reduced to 6.9 +/- 0.7 mmol l-1 (p less than 0.001). During the insulin infusion, capillary blood velocity increased by 28.8% (p less than 0.05), and the diameter of the capillary erythrocyte column increased from 7.6 +/- 0.2 to 9.2 +/- 0.3 micron (p less than 0.01). Thus during the insulin infusion, the calculated capillary flow increased to 226 +/- 36% above basal values (p less than 0.01). Laser Doppler flow did not change significantly, suggesting that during insulin infusion skin blood flow is redistributed with an increase in capillary flow relative to arteriovenous shunt flow.     

Beneficial effect of a low glycaemic index diet in type 2 diabetes.

Low glycaemic index foods produce low blood glucose and insulin responses in normal subjects, and improve blood glucose control in Type 1 and well-controlled Type 2 diabetic patients. We studied the effects of a low glycaemic index diet in 15 Type 2 diabetic patients with a mean fasting blood glucose of 9.5 mmol l-1 using a randomized, crossover design. Patients were given pre-weighed diets (59% energy as carbohydrate, 21% fat, and 24 g 1000-kcal-1 dietary fibre) for two 2-week periods, with a diet glycaemic index of 60 during one period and 87 during the other. On the low glycaemic index diet, the blood glucose response after a representative breakfast was 29% less than on the high glycaemic index diet (874 +/- 108 (+/- SE) vs 204 +/- 112 mmol min l-1; p less than 0.001), the percentage reduction being almost identical to the 28% difference predicted from the meal glycaemic index values. After the 2-week low glycaemic index diet, fasting serum fructosamine and cholesterol levels were significantly less than after the high glycaemic index diet (3.17 +/- 0.12 vs 3.28 +/- 0.16 mmol l-1, p less than 0.05, and 5.5 +/- 0.4 vs 5.9 +/- 0.5 mmol l-1, p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral magnesium supplementation in insulin-requiring Type 2 diabetic patients

Oral magnesium (Mg) supplementation can improve insulin sensitivity and secretion in patients with Type 2 diabetes mellitus (DM). We studied the effect of Mg supplementation on glycaemic control, blood pressure, and plasma lipids in insulin-requiring patients with Type 2 DM. Fifty moderately controlled patients were randomized to 15 mmol Mg or placebo daily for 3 months. Plasma Mg, glucose, HbA_1c, lipids, erythrocyte Mg, Mg and glucose concentrations in 24-h urine, and systolic and diastolic pressure were measured before and after 3 months treatment. Plasma Mg concentration was higher after supplementation than after placebo (0.82 ± 0.07 vs 0.78 ± 0.08 mmol l⁻¹, p<0.05), as was Mg excretion (5.5 ± 1.9 vs 3.7 ± 1.4 mmol 24 h⁻¹, p = 0.004) but erythrocyte Mg concentrations were similar. No significant differences were found in glycaemic control (glucose: 10.7 ± 3.8 vs 11.6 ± 6.2 mmol l⁻¹, p = 0.8; HbA_1c: 8.9 ± 1.6 vs 9.1 ± 1.2%, p = 0.8), lipids or blood pressure. On-treatment analysis (34 patients: 18 on Mg, 16 on placebo) yielded similar results. An increase in plasma Mg concentration irrespective of medication was associated with a tendency to a decrease in diastolic pressure (increased plasma Mg vs no increase: −4.0 ± 10.1 vs +2.5 ± 12.0 mmHg, p = 0.059). Three months’ oral Mg supplementation of insulin-requiring patients with Type 2 DM increased plasma Mg concentration and urinary Mg excretion but had no effect on glycaemic control or plasma lipid concentrations. © 1998 John Wiley & Sons, Ltd.     

Determination and kinetic analysis of non-insulin mediated glucose uptake in Type 1 (insulin-dependent) diabetes mellitus

Summary In man, total glucose uptake is the sum of insulin mediated glucose uptake and non-insulin mediated glucose uptake. The latter pathway has not been examined in Type 1 (insulin-dependent) diabetes mellitus. In order to assess non-insulin mediated glucose uptake in Type 1 diabetes, we measured steady-state rates of glucose uptake during glucose clamps at 5.27, 9.71 and 12.5 mmol/l using low (0.25 mU· kg^–1·min^–1), intermediate (0.75 mU·kg^–1·min^–1) and high (1.50 mU·kg^–1·min^–1) insulin infusion rates in 10 subjects with Type 1 diabetes. For insulin infusion rates of 0.25, 0.75 and 1.50 mU·kg^–1·min^–1 as plasma glucose rose from 5.27 to 9.71 mmol/l, total glucose uptake increased by 35, 43 and 52 percent respectively (p<0.05 for each insulin infusion rate). For all three insulin infusion rates, there was no significant increase in total glucose uptake as plasma glucose increased from 9.71 to 12.5 mmol/l. At each glycaemic level, glucose uptake correlated significantly with plasma free insulin (r=0.81, p<0.01 at 5.71 mmol/l; r=0.84, p<0.01 at 9.71 mmol/l; r=0.73, p<0.02 at 12.5 mmol/l). Linear regression analysis to a point corresponding to plasma free insulin equalling zero, yielded values for non-insulin mediated glucose uptake (mmol·kg^–1·min^–1) of 0.11,0.14,0.18 at plasma glucose of 5.27, 9.7 and 12.5 mmol/l respectively. Thus, increasing plasma glucose concentrations were associated with increasing rates of non-insulin mediated glucose uptake. For each insulin infusion rate used, the percent of total glucose uptake accounted for by non-insulin mediated glucose uptake remained independent of plasma glucose concentration, but decreased as insulin infusion rate increased. During the insulin infusion at 0.25 mU·kg^–1·min^–1, this percentage ranged from 83.7 to 91.4%. Analysis of glucose uptake data derived for theoretical plasma insulin levels of 0, 40, 80 and 160 U/ml yielded linear Eadie-Hofstee plots (r=– 0.83 to – 0.99), suggesting that insulin increased Vmax but did not alter Km. Hence, in these subjects with Type 1 diabetes, glucose uptake, both insulin mediated and non-insulin mediated can be described by Michaelis-Menten kinetics. Comparison of values obtained for Vmax and Km in the present studies of Type 1 diabetes with those obtained from non-diabetic subjects indicates that non-insulin dependent glucose uptake in Type 1 diabetes is quantitatively similar to that of non-diabetic subjects.     

Managing hyperglycaemia during antenatal steroid administration,labour and birth in pregnant women with diabetes

Optimal glycaemic control before and during pregnancy improves both maternal and fetal outcomes. This article summarizes the recently published guidelines on the management of glycaemic control in pregnant women with diabetes on obstetric wards and delivery units produced by the Joint British Diabetes Societies for Inpatient Care and available in full at www.diabetes.org.uk/joint-british-diabetes-society and https://abcd.care/joint-british-diabetes-societies-jbds-inpatient-care-group . Hyperglycaemia following steroid administration can be managed by variable rate intravenous insulin infusion (VRIII) or continuous subcutaneous insulin infusion (CSII) in women who are willing and able to safely self‐manage insulin dose adjustment. All women with diabetes should have capillary blood glucose (CBG) measured hourly once they are in established labour. Those who are found to be higher than 7 mmol/l on two consecutive occasions should be started on VRIII. If general anaesthesia is used, CBG should be monitored every 30 min in the theatre. Both the VRIII and CSII rate should be reduced by at least 50% once the placenta is delivered. The insulin dose needed after delivery in insulin‐treated Type 2 and Type 1 diabetes is usually 25% less than the doses needed at the end of first trimester. Additional snacks may be needed after delivery especially if breastfeeding. Stop all anti‐diabetes medications after delivery in gestational diabetes. Continue to monitor CBG before and 1 h after meals for up to 24 h after delivery to pick up any pre‐existing diabetes or new‐onset diabetes in pregnancy. Women with Type 2 diabetes on oral treatment can continue to take metformin after birth.     

Prandial Glycaemia After a Carbohydrate-rich Meal in Type I Diabetic Patients: Using the Rapid Acting Insulin Analogue [Lys(B28), Pro(B29)] Human Insulin

The time–action profile of the insulin analogue insulin lispro ([Lys(B28), Pro(B29)] human insulin) with its rapid onset and short duration of action might be more suitable to limit hyperglycaemic excursions after a meal rich in rapidly absorbable carbohydrates in comparison to regular human insulin. A randomized, double-blind study was performed in 10 Type I diabetic patients with good metabolic control (HbA_1c 7.0 ± 0.5 %). After a baseline period of 3 h (blood glucose clamped at 6.7 mmol l⁻¹, i.v. insulin infusion of 0.2 mU kg⁻¹ min⁻¹ throughout the study), the patients ate a pizza, drank a cola and had a carbohydrate-rich dessert (total carbohydrate content 140 g). Immediately before the meal 15.4 ± 3.5 U of either insulin preparation were injected subcutaneously. Blood glucose concentrations were monitored continuously thereafter. Following the injection of insulin lispro the area under the blood glucose curve after the meal was 78 % of that of regular insulin (1.76 ± 0.34 vs 2.26 ± 0.68 mol l⁻¹ *240 min⁻¹; p < 0.01). Maximal blood glucose excursions were higher and were reached later after regular insulin as compared to insulin lispro (11.9 ± 2.8 vs 9.9 ± 1.4 mmol l⁻¹; p < 0.05; 66 ± 37 vs 41 ± 7 min; p < 0.05). Maximal individual differences in the blood glucose excursions (regular human insulin minus insulin lispro) were 4.8 ± 2.2 mmol l⁻¹ (p < 0.0001 against zero) after 110 ± 37 min. In Type I diabetic patients prandial blood glucose excursions after a carbohydrate rich meal were reduced after preprandial injection of insulin lispro in comparison to human regular insulin.     

Beta Cell Response to Oral Glimepiride Administration During and Following a Hyperglycaemic Clamp in NIDDM Patients

The aim of the present study was to assess the beta cell response to glimepiride, administered orally, during and following a hyperglycaemic clamp in 14 NIDDM patients (7 males), aged 62.5 (St. Dev. 7.7) years with a body mass index of 27.3 (2.8) kg m⁻² and HbA_lc of 7.0 (0.7) % at baseline, in a placebo controlled study. All patients were on stable treatment with a second generation sulphonylurea for at least 8 weeks prior to randomization and received placebo (P) or 5 mg glimepiride (G) daily for 7 days and 10 mg prior to a hyperglycaemic clamp (10.9 mmol l⁻¹ for 60 min, preceded by i.v. insulin infusion to stablize fasting blood glucose levels at 4.0 mmol l⁻¹). The clamp was followed by an observation period of 2 h in 5 subjects and 3.5 h in the next 9 subjects, during which blood glucose and plasma insulin, C-peptide and proinsulin levels were measured at regular intervals to determine the effect of glimepiride on the interaction between changes in glycaemia and plasma levels of beta cell products. Neither G nor P elicited a first phase insulin response. Areas under plasma insulin curve during the 1 h hyperglycaemic clamp were 94.2 (39.5) vs 69.1 (26.5) pmol.h l⁻¹ in G and P clamps, respectively (p = 0.002). Total areas (AUC) under the plasma insulin curve were 377 (145) vs 271 (113) pmol.h l⁻¹ in G and P clamps (< 0.05). Total AUCs of C-peptide were 309 (96) and 259 (102 pmol.h.⁻¹, in G and P clamps, respectively, p = 0.01. Total AUCs of proinsulin were 176 (77) versus 119 (56) pmol.h l⁻¹ in G and P clamps, respectively, p = 0.004. Five hours after G and P administration blood glucose levels were 4.7) 92.1) mmol⁻¹ in the G clamp vs 6.2 (1.9) mmol l⁻¹ in the P clamp (p = 0.001). The number of hypoglycaemic events (blood glucose < 3.0 mmol l⁻¹) in the 3.5 h observation period was 3 in G clamps vs 0 in P clamps (p = ns). In conclusion, glimepiride stimulates the second phase insulin and proinsulin secretion. The lowering of blood glucose levels is not accompanied by a commensurate inhibition of the insulin secretion. Further studies are required to compare this new drug with currently available oral hypoglycaemic agents, with respect to glycaemic control and the risk of hypoglycaemia. © 1997 John Wiley & Sons, Ltd.     

Beta-cell Dysfunction in First-degree Relatives of Patients with Non-insulin-dependent Diabetes Mellitus

To analyse the relationship between age, glucose tolerance, beta-cell function, and insulin sensitivity in preclinical states of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), we have done a cross-sectional, age-stratified analysis of 86 non-diabetic first-degree relatives of NIDDM patients and 49 controls with similar age, sex, and BMI. A 5 mg kg ideal body weight⁻¹ min⁻¹ for 60 min of continuous infusion of glucose with model assessment (CIGMA) of serum glucose and C-peptide values at the end of the infusion was used to determine glucose tolerance and beta-cell function. Insulin sensitivity was estimated by modelling basal serum glucose and insulin values. Relatives and controls were divided into tertiles on the basis of age. Relatives had higher basal (5.3 vs 5 mmol l⁻¹, p = 0.02) and achieved serum glucose (9.1 vs 8.4 mmol l⁻¹, p = 0.01), lower beta-cell function (128 vs 145 %, p = 0.007), and lower insulin sensitivity (37 vs 43 %, p = 0.002). Beta-cell function declined with age in relatives (from 139 % in young subjects to 134 % in intermediate subjects and to 111 % in older subjects, p = 0.002) and this decline was associated with an increase in basal serum glucose (from 5.1 to 5.3 and to 5.7 mmol l⁻¹, p = 0.000) and achieved glucose (from 8.3 to 9.1 and to 9.3 mmol l⁻¹, p = 0.038), without significant changes in insulin sensitivity. These trends were observed even after the exclusion of subjects with mild glucose intolerance. We conclude that both beta-cell dysfunction and insulin resistance are present in first-degree relatives of NIDDM. The progression of beta-cell dysfunction and glucose intolerance with age suggests that beta-cell dysfunction is the key factor in the apparition and progression of the disease.     

The Short Insulin Tolerance Test: Feasibility Study Using Venous Sampling

The short insulin tolerance test (ITT) is both a simple and valid method of quantifying insulin sensitivity although arterialization of samples and the risk of hypoglycaemia remain as potential difficulties. We examined the safety and reproducibility of using venous sampling with insulin doses of 0.1U kg⁻¹ and 0.05 U kg⁻¹ in healthy subjects. Whole blood glucose concentrations were measured contemporaneously and the rate of plasma glucose decline (mmol l⁻¹ min⁻¹) for each test was estimated from unlogged venous plasma glucose concentrations measured at 1 min intervals. The mean rates of plasma glucose decline for the 0.1 U kg⁻¹ and 0.05 U kg⁻¹ insulin doses were 0.26 mmol l⁻¹ min⁻¹ (n = 11, range = 0.17–0.41, intrasubject coefficient of variation (CV) = 9.4%) and 0.25 mmol l⁻¹ min⁻¹ (n = 6, range 0.19–0.46, intrasubject CV = 15.9%), respectively. Reversal of significant hypoglycaemia was necessary in one subject before 15 min post-insulin. We found that: (1) venous sampling provides a reproducible measure of glucose uptake after insulin, (2) contemporaneous bedside glucose sampling identifies those at risk of significant hypoglycaemia during the ITT, and (3) the 0.1 U kg⁻¹ dose response is more reproducible and no less safe than the half dose response. We conclude that the current ITT protocol would be made safer and simpler with the above modifications although further studies comparing venous with arterialized sampling are needed.     

Nocturnal Blood Glucose Profiles in Patients with Type 1 Diabetes Mellitus on Multiple (≥4) Daily Insulin Injection Regimens

The aim of the study was to examine nocturnal blood glucose profiles in Type 1 diabetic patients on multiple (⩾4) daily insulin injections. Nocturnal blood glucose profiles were evaluated in 31 patients collecting blood samples half-hourly from 23.00 till 07.30 h, while they were asleep. Nocturnal episodes of hypoglycaemia (blood glucose <3.0 mmol l⁻¹) occurred in 29 % of these nights; 67 % of episodes were asymptomatic. In the early night (23.00–01.00 h), five episodes occurred with a median duration of 1 h. In the early morning (04.00–07.30 h) seven episodes occurred with a median duration of 3 h. No hypoglycaemia was noted from 01.00 to 04.00 h. Bedtime glucose levels appeared to predict ‘early night’ hypoglycaemia but not ‘early morning’ hypoglycaemia. Fasting glucose levels <5.5 mmol l⁻¹ were indicative of preceding ‘early morning’ hypoglycaemia. There was a large intra-individual variation in nocturnal blood glucose profiles. It is concluded that daily monitoring of bedtime and fasting blood glucose levels may be both more reliable and convenient for the prevention of nocturnal hypoglycaemia than periodic testing of blood glucose at 03.00h as is often advised. Setting a target of >5.5 mmol l⁻¹ for fasting blood glucose may decrease the frequency of nocturnal hypoglycaemia.     

‘Hospital Hyperglycaemia’; Perception or Reality?

Patients' perceptions that clinic fasting blood glucose measurements in Type 2 diabetes are artefactually high were investigated. Eighteen men and 14 women in the Salford cohort of the United Kingdom Prospective Diabetes Study (UKPDS) with a median age of 51 (range 37–69) years measured their fasting blood glucose concentration at home with visually read sticks or meters; they then collected capillary blood into fluoride tubes both at home and in clinic after a median lapse of 77 (range 25–173) min. The clinic samples were measured immediately and after a time lapse equivalent to the time taken to reach clinic to control for continued glycolysis in the home sample. Mean fasting blood glucose was 5.9 ± 1.9 mmol 1^-1 by the patients' own measurement and 6.0 ± 1.8 mmol 1^-1 on the home collected sample compared with 6.2 ± 2.0 mmol 1^-1 and 6.1 ± 2.0 mmol 1^-1 on the hospital immediate and time-lapsed measurements, respectively (p > 0.05 for all comparisons between home and hospital measurements); although there were no systematic differences, occasional measurements differed more than 2 mmol 1^-1. These data support the use of the fasting blood glucose level as a stable, patient-independent measure of glycaemic control in Type 2 diabetes     

The use of low glycaemic index foods improves metabolic control of diabetic patients over five weeks.

The aim of the present study was to determine whether any benefit might occur from lowering the glycaemic index of diet in the medium term in diabetic patients. Eighteen well-controlled diabetic patients (12 Type 1 and 6 Type 2 non-insulin-treated), were assigned to either a high mean glycaemic index or low mean glycaemic index diet for 5 weeks each in a random order using a cross-over design. The two diets were equivalent in terms of nutrient content and total and soluble fibre content. The glycaemic indices were 64 +/- 2 (mean +/- SD) % and 38 +/- 5% for the two diets. The high glycaemic index diet was enriched in bread and potato and the low glycaemic index diet in pasta, rice, and legumes. At the end of the study periods, the following variables were improved on the low compared to the high glycaemic index diet: fructosamine (3.9 +/- 0.9 vs 3.4 +/- 0.4 mmol l-1, p less than 0.05); fasting blood glucose (10.8 +/- 2.8 vs 9.6 +/- 2.7 mmol l-1, p less than 0.02); 2-h postprandial blood glucose (11.6 +/- 2.9 vs 10.3 +/- 2.5 mmol l-1, p less than 0.02); mean daily blood glucose (12.0 +/- 2.5 vs 10.4 +/- 2.7 mmol l-1, p less than 0.02); serum triglycerides (1.5 +/- 0.9 vs 1.2 +/- 0.6 mmol l-1, p less than 0.05). No significant differences were found in body weight, HbA1C, insulin binding to erythrocytes, insulin and drug requirements, and other circulating lipids (cholesterol, HDL-cholesterol, phospholipids, Apolipoprotein A1, Apolipoprotein B). Thus the inclusion of low glycaemic index foods in the diet of diabetic patients may be an additional measure which slightly but favourably influences carbohydrate and lipid metabolism, requires only small changes in nutritional habits and has no known deleterious effects.     

Glycaemic control in type 1 diabetic patients using optimised insulin aspart or human insulin in a randomised multinational study

Insulin aspart (IAsp), is a rapid-acting analogue of human insulin (HI), for use in the meal related treatment of diabetes mellitus. The degree of glycaemic control achieved by IAsp in comparison with HI after algorithm-driven dose optimisation was tested over 3 months. The prospective, multicentre, randomised, open-label study with parallel groups was performed in 48 centres in 11 countries and included 423 basal-bolus treated patients with Type 1 diabetes. Main outcome measures were blood glucose control assessed by HbA1c, nine-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia and adverse events. An algorithm-driven increase occurred in the dose and number of daily injections of basal insulin, particularly in the IAsp group. After 12 weeks of treatment, HbA1c was significantly lower in IAsp compared to HI treated subjects by 0.17 (95% CI 0.30-0.04) (P<0.05). Comparison of the blood glucose profiles showed lower blood glucose levels with IAsp after breakfast (mean 8.4 vs 10.1 mmol/l; P<0.0001) and dinner (8.2 vs 9.3 mmol/l; P<0.01). There were no differences between treatments in the incidence of hypoglycaemic episodes or in the adverse event profiles. The WHO Diabetes Treatment Satisfaction Questionnaire score for perceived hyperglycaemia was lower with Iasp (P=0.005), and patients found the insulin aspart treatment more flexible (P=0.022). The current study underlines the need for optimising the basal insulin regimen in order to take full advantage of the pharmacodynamics of IAsp.     

Acute and chronic effects of hyperglycaemia on glucose metabolism

Summary In normal man, several hormonal and metabolic adjustments allow the maintenance of the blood glucose concentration within narrow limits. Hyperglycaemia participates in this regulation via stimulation of glucose disposal and inhibition of glucose production. The effects are mediated, in addition to changes in insulin and glucagon secretion, by the mass-action effect of glucose. In both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients, hyperglycaemia, by mass-action abnormally elevates the basal glucose utilization rate but compensates for reduced postprandial insulin-stimulated glucose disposal. When exposed to chronic hyperglycaemia, the body tissues seem to protect themselves, at least partly, against excessive glucose utilization. These protective mechanisms include both a reduction in insulin stimulated glucose disposal and insulin secretion. Chronic hyperglycaemia may also reduce non-insulin-dependent glucose utilization, at least in rats. In Type 1 diabetic patients with normal peripheral insulin concentrations, chronic hyperglycaemia per se could be a major cause of insulin resistance. In Type 2 diabetic patients, insulin resistance is often already present before the development of overt fasting hyperglycaemia. At the diabetic stage, hyperglycaemia could, however, maintain a self-perpetuating cycle, where the deleterious effects of high glucose concentrations on insulin action and secretion cause further deterioration of glycaemic control. The biochemical basis for hyperglycaemia-induced insulin resistance is still far from clear, but could involve changes in the glucose transporter number and gene expression.     

Adding metformin versus insulin dose increase in insulin-treated but poorly controlled Type 2 diabetes mellitus: an open-label randomized trial

To compare the effect of adding metformin to insulin therapy with a moderate increase in insulin dose alone in insulin-treated, poorly controlled Type 2 diabetic patients, 47 consecutive such patients (baseline daily dose >0.5 IU kg⁻¹ and HbA_1c >8 %) were openly randomized either to a combination of their previous insulin schedule plus metformin (2.55 g daily in three divided doses, n = 24) or to a moderate insulin dose increase (20 % of baseline, n = 23). The patient status/biochemical profile was assessed at entry and at 4 months. Among those assigned to insulin + metformin, 18 took the drug. Upon an intention-to-treat basis, patients assigned to insulin dose increase had a statistically significant weight gain (1.16 + 1.9 vs 0.3 ± 4.5 kg, p < 0.05). Patients assigned to the insulin + metformin regimen experienced a significantly greater fall in HbA_1c (−1.87 ± 2.16 vs 0.03 ± 1.68 %, p < 0.01), total cholesterol (−0.56 ± 0.89 vs 0.14 ± 0.72 mmol l⁻¹, p < 0.05) and LDL-cholesterol (−0.51 ± 0.73 vs 0.19 ± 0.6 mmol l⁻¹, p < 0.01). These data suggest that adding metformin to insulin in poorly controlled Type 2 DM patients offers an advantage in terms of glycaemic control and lipid plasma profile. Copyright © 1998 John Wiley & Sons, Ltd.     

A protocol for improved glycaemic control following corticosteroid therapy in diabetic pregnancies.

AIMS: Diabetic pregnancies have an increased risk of respiratory distress syndrome (RDS) and preterm delivery. Antenatal corticosteroids can prevent RDS but induce acute severe hyperglycaemia. We have developed a protocol which prevents hyperglycaemia and can be used easily by ward staff. METHODS: Intramuscular dexamethasone is given in two doses 12 h apart. Subcutaneous insulin and diet are continued but from the first dexamethasone dose until 12 h after the second, supplementary intravenous insulin is infused according to hourly blood glucose measurements. The protocol incorporates four graded sliding scales. The initial scale is selected according to the patient's current subcutaneous insulin dose and advanced if the blood glucose is > or = 10.1 mmol/l for 2 consecutive hours. RESULTS: In a 10-month period eight (three gestational, five pre-gestational) women received antenatal corticosteroids from a total of 37 diabetic pregnancies. The median amount of supplementary intravenous insulin required was 74 U (range 32-88 U); the median glucose values achieved were 5.8-8.9 mmol/l. Seventy-five percent of glucose measurements were within an acceptable range of 4-10 mmol/l. Only one baby developed RDS. DISCUSSION: Large amounts of supplementary intravenous insulin are needed to achieve even moderate glycaemic control. This protocol enables routine ward staff to manage this successfully.