Showing papers in "Diabetic Medicine in 1998"

Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.

Abstract: The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.

UKPDS 26: sulphonylurea failure in non‐insulin‐dependent diabetic patients over six years

Abstract: Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphonylureas 'fail'. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulphonylureas, we report on the responses in 1305 patients with newly diagnosed Type 2 DM randomly allocated to therapy with either chlorpropamide or glibenclamide in the UK Prospective Diabetes Study (UKPDS). These patients were initially treated by diet for 3 months and had a fasting plasma glucose > 6 mmol l(-1); mean age 53 (SD 9) years; BMI 26.8 (SD 5.0) kg m(-2); and median fasting plasma glucose 9.1 (7.6-12.5 quartiles) mmol l(-1). If their fasting plasma glucose subsequently rose above 15.0 mmol l(-1), or they developed hyperglycaemic symptoms, additional hypoglycaemic therapy was given: metformin, ultratard insulin, and soluble insulin as required. By 6 years, 44% had required additional therapy. Of those randomized to glibenclamide, 48% required additional therapy by 6 years, compared with 40% of those allocated to chlorpropamide (p or = 10.0 mmol l(-1), > or = 7.8 mmol l(-1) to or = 30 kg m(-2)) (43% vs 53% at 6 years; p < 0.001). Modelled beta-cell function showed that those with lower function were more likely to fail (p < 0.0001). Thus sulphonylureas fail as a therapeutic agent at rates which are dependent both on the phenotype at presentation and perhaps on the agent used initially. Higher failure rates were found in those with higher glucose concentrations, those who were younger, those with lower beta-cell reserve and those randomized to glibenclamide compared with chlorpropamide.

Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy

Abstract: Guidelines on the out-patient management of diabetic peripheral neuropathy have been developed from an international consensus meeting attended by diabetologists, neurologists, primary care physicians, podiatrists and diabetes specialist nurses. A copy of the full document follows this summary (Appendix 1). The document arose out of suggestions from Neurodiab, a subgroup of the European Association for the Study of Diabetes, that there was a need for guidelines developed by consensus, for the outpatient management of patients with diabetic neuropathy. An international consensus group was created, chaired by two of the authors. A pilot working party met in 1995, followed by a full working party of 39 experts, neurologists and diabetes physicians (Appendix 2). This compiled a draft guideline document which was circulated to a number of international bodies. After consultation with its members, the final guidelines were approved by Neurodiab (chairman F.A. Gries) towards the end of 1997. © 1998 John Wiley & Sons, Ltd.

Maturity-onset diabetes of the young: clinical heterogeneity explained by genetic heterogeneity.

Abstract: Maturity-onset diabetes of the young (MODY) can be defined by the clinical characteristics of early-onset Type 2 (non-insulin-dependent) diabetes and autosomal dominant inheritance. Mutations in four genes have been shown to cause MODY: glucokinase, hepatic nuclear factor 1 alpha (HNF1alpha), hepatic nuclear factor 4 alpha (HNF4alpha) and insulin promoter [corrected] factor 1 (IPF1). In white Caucasians it is now possible to define the gene in most patients with a clinical diagnosis of MODY. Each gene involved in MODY has its own specific clinical and physiological characteristics. Patients with mutations of the glucokinase gene have mild fasting hyperglycaemia throughout life, and rarely require medication or develop microvascular complications. The principle pathophysiology is stable beta-cell dysfunction characterized by reduced sensing of glucose by the pancreas. Patients with mutations in HNF1alpha have normal glucose tolerance in early childhood and usually present with symptomatic diabetes in their late teens or early adulthood. They show increasing hyperglycaemia and treatment requirements with frequent microvascular complications. The underlying defect is progressive beta-cell failure, with the early lesion characterized by failure to increase insulin secretion with increasing glucose levels. Patients with HNF4alpha and IPF1 mutations show a similar clinical picture to HNF1alpha although diabetes may be diagnosed later. There are other patients with MODY in whom the genetic defect is still unknown. Molecular genetic testing in patients with diabetes offers the possibility of making a firm diagnosis of MODY and allows prediction of the future clinical course. The role of predictive testing in non-diabetic subjects within families is uncertain at present. Preliminary evidence suggests that maintaining insulin sensitivity by avoiding obesity and regular physical exercise may help delay the onset of diabetes.

Size at birth, maternal weight, and type 2 diabetes in South India.

Abstract: Recent research in Europe and the USA has shown that adults who had a low birthweight or who were thin at birth with a low ponderal index (birthweight/length3) tend to be insulin resistant and have an increased risk of developing Type 2 diabetes mellitus. Low birthweight and Type 2 diabetes are common in India. We have studied glucose and insulin metabolism in 506 men and women (aged 39-60 years) born in a hospital in Mysore, South India, which kept detailed obstetric records from 1934. The prevalence of Type 2 diabetes was 15%. In contrast to Western populations, higher rates were found in men and women who were short at birth (p = 0.07) and had a high ponderal index (p = 0.05). Their mothers tended to be heavier than average during pregnancy (p = 0.004). Higher ponderal index at birth was also associated with a lower 30 minute insulin increment (p = 0.009), a marker of reduced beta cell function. We speculate that the rise in Type 2 diabetes in Indian urban populations may have been triggered by mild obesity in mothers, leading to glucose intolerance during pregnancy, macrosomic changes in the fetus, and insulin deficiency in adult life.

Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study.

Abstract: Secondary failure of plasma glucose control following initial successful response to diet therapy may be due to dietary indiscretion, or to progression of the intrinsic diabetic condition. We report a 10-year prospective natural history study of 432 newly diagnosed diabetic patients aged 40–69 years undertaken to assess the effect of intensive dietary management, where patients were transferred to insulin, or oral hypoglycaemic therapy (tolbutamide, metformin) by predetermined criteria of weight and plasma glucose. Secondary failure to diet therapy occurred in 41 patients in years 2–4, 67 patients in years 5–7, and 51 patients in years 8–10; 173 patients remained on diet alone until death or the end of the study. Continuation on diet alone was associated with a lower ongoing fasting plasma glucose, greater beta-cell function assessed by an oral glucose tolerance test at 6 months, and increasing age. The rate of rise of fasting plasma glucose was inversely related to the duration of successful dietary therapy, but mean weight remained constant in all groups while on diet alone. The ongoing fall in beta-cell function assessed by HOMA modelling closely mirrored the progressive rise in fasting plasma glucose: there was no change in mean insulin sensitivity in any of the groups. © 1998 John Wiley & Sons, Ltd.

Insulin management and metabolic control of Type 1 diabetes mellitus in childhood and adolescence in 18 countries

Abstract: Insulin regimens and metabolic control in children and adolescents with Type 1 diabetes mellitus were evaluated in a cross-sectional, non-population-based investigation, involving 22 paediatric departments, from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from 2873 children from March to August 1995. HbA1c was determined once and analysed centrally (normal range 4.4–6.3 %, mean 5.4 %). Year of birth, sex, duration of diabetes, height, body weight, number of daily insulin injections, types and doses of insulin were recorded. Average HbA1c in children under 11 years was 8.3 ± 1.3 % (mean ± SD) compared with 8.9 ± 1.8 % in those aged 12–18 years. The average insulin dose per kg body weight was almost constant (0.65 U kg−124 h−1) in children aged 2–9 years for both sexes, but there was a sharp increase during the pubertal years, particularly in girls. The increase in BMI of children with diabetes was much faster during adolescence compared to healthy children, especially in females. Sixty per cent of the children (n = 1707) used two daily insulin injections while 37 % (n = 1071) used three or more. Of those on two or three injections daily, 37 % used pre-mixed insulins, either alone or in combination with short- and intermediate-acting insulin. Pre-adolescent children on pre-mixed insulin showed similar HbA1c levels to those on a combination of short- and long-acting insulins, whereas in adolescents significantly better HbA1c values were achieved with individual combinations. Very young children were treated with a higher proportion of long-acting insulin. Among adolescent boys, lower HbA1c was related to use of more short-acting insulin. This association was not found in girls. We conclude that numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards intensive diabetes management, particularly in older adolescents. Nevertheless, the goal of near normoglycaemia is achieved in only a few. © 1998 John Wiley & Sons, Ltd.

Mortality and morbidity from diabetes in South Asians and Europeans: 11-year follow-up of the Southall Diabetes Survey, London, UK.

Abstract: Over 20% of middle aged and elderly South Asian people throughout the world have diabetes. The associated mortality and morbidity risks are unclear. We compared mortality and morbidity in a cohort of South Asian and European people with diabetes in London, UK, in an 11-year follow-up of a population-based sample of 730 South Asians (mean age 55 in 1984) and 304 Europeans (mean age 67 in 1984) with diabetes aged 30 years and above in 1984. By 1995, 242 (33%) of South Asians, and 172 (57%) of Europeans had died. The all-cause mortality rate ratio (South Asian versus European) was 1.50 (95% CI 0.72-3.12) for those aged 30-54 years at baseline. Ethnic differences in mortality rates were abolished or reversed in people aged 65 years and above at baseline. The mortality rate ratio for circulatory deaths was 1.80 (95% CI 1.03-3.16, p < 0.05) and for heart disease was 2.02 (95% CI 1.04-3.92, p < 0.05) in those aged 30-64 years at baseline. Seventy-seven per cent of South Asian deaths were caused by circulatory disease, compared with 46% of European deaths. South Asian survivors were 3.8 times (95% CI 1.8-8.0, p = 0.001) more likely to report a history of myocardial infarction than Europeans. South Asian adults with diabetes show a markedly increased predisposition to cardiovascular disease compared with Europeans, especially in younger people. This emphasizes the urgent need to reduce cardiovascular risk in this vulnerable group.

Evaluation of a diabetic foot screening and protection programme

Abstract: We set out to evaluate a clinical foot-screening programme in terms of primary outcomes (reductions in the incidence of ulcers and lower limb amputation) and process outcomes (compliance with screening, the number of patients not completing the programme and the use of chiropody services and prescribed footwear and cost). All but 4 of 2001 patients attending a general diabetic out-patient clinic were allocated randomly to index and control groups. The exceptions were patients who presented with active ulcers and were placed in the index group. Primary and secondary screening programmes identified 128 high risk patients in the index group and these were admitted to the foot protection programme. At 2-year follow-up, 11 fewer ulcers were reported from the index group. There were 7 amputations (1 major, 6 minor) in the index group and 23 (12 major and 13 minor) in the control group. The differences were not statistically significant for ulceration or minor amputations but significant for major amputations (p < 0.01). The total cost of the 2-year programme was pounds sterling 100,372 (1991-92 costs), with a mean cost per patient of approximately pounds sterling 100. Taking pounds sterling 12,000 as a conservative estimate of the cost of a major amputation, the foot clinic was cost-effective in terms of amputations averted. The process outcomes were much less satisfactory. Cost-effectiveness could have been improved if it had been possible to improve patient compliance.

Conservative surgical approach versus non‐surgical management for diabetic neuropathic foot ulcers: a randomized trial

Abstract: To test the efficacy of surgical treatment of non-infected neuropathic foot ulcers compared to conventional non-surgical management, a group of diabetic outpatients attending our diabetic foot clinic were studied. All patients who came to the clinic for the first time from January to December 1995 inclusive with an uncomplicated neuropathic ulcer were randomized into two groups. Group A received conservative treatment, consisting of relief of weight-bearing, regular dressings; group B underwent surgical excision, eventual debridement or removal of bone segments underlying the lesion and surgical closure. Healing rate, healing time, prevalence of infection, relapse during a 6-month period following intervention and subjective discomfort were assessed. Twenty-four ulcers in 21 patients were treated in group A (17 Type 2 DM/3 Type 1 DM, age 63.24 +/- 13.46 yr, duration of diabetes 18.2 +/- 8.41 yr, HbA1c 9.5 +/- 3.8%) and 22 ulcers in 21 patients in group B (19 Type 2 DM/2 Type 1 DM, age 65.53 +/- 9.87yr, duration of diabetes 16.84 +/- 10.61 yr; HbA1c 8.9 +/- 2.2%). Healing rate was lower (79.2% = 19/24 ulcers) in group A than in group B (95.5% = 21/22 ulcers; p < 0.05), and healing time was longer (128.9 +/- 86.60 days vs 46.73 +/- 38.94 days; p < 0.001). Infective complications occurred significantly more often in group A patients (3/24, 12.5% vs 1/22, 4.5%; p < 0.05), as did relapses of ulcerations (8 vs 3; p < 0.01). There were only two minor perioperative complications in group B patients. Patients reported a higher degree of satisfaction in group B (p < 0.01) as well as lower discomfort (p < 0.05) and restrictions (p < 0.05). Thus surgical treatment of neuropathic foot ulcers in diabetic patients proved to be an effective approach compared to conventional treatment in terms of healing time, complications, and relapses, and can be safely performed in an outpatient setting.

Type 1 diabetes mellitus and Down's syndrome: prevalence, management and diabetic complications

Abstract: Type 1 insulin-dependent, diabetes mellitus (Type 1 DM) is thought to be more prevalent in individuals with Down's syndrome. To ascertain the local prevalence of Type 1 DM in patients with Down's syndrome in a geographically defined area, the four diabetes clinics in Lothian were surveyed and 13 patients with Down's syndrome and Type 1 DM were identified. Using data from previous epidemiological surveys which determined the prevalence of Down's syndrome in the general population, the prevalence rate of Type 1 DM in patients with Down's syndrome was calculated to be between 1.4 and 10.6%, a prevalence considerably higher than in the general population. Although 7 (54%) of the Down's syndrome patients were treated with once daily administration of insulin, the mean HbA1c value of the group was similar to that observed in a control group of 39 age-, sex- and duration-matched Type 1 patients, all of whom were taking two or more injections of insulin daily. Glycaemic control was therefore of similar quality to matched Type 1 patients without Down's syndrome, despite the frequent use of simple insulin regimens, which may relate to the more stable lifestyle of these patients.

The postprandial state and risk of cardiovascular disease

Abstract: Metabolism in man is regulated by complex hormonal signals and substrate interactions, and for many years the clinical focus has centred on the metabolic and hormonal picture after an overnight fast. More recently, the postprandial state, i.e. ‘the period that comprises and follows a meal’, has received more attention. The oral glucose tolerance test (OGTT), although highly non-physiological, has been used largely as a model of the postprandial state. Epidemiological studies have shown that, when ‘impaired’, oral glucose tolerance is associated with an increased risk of cardiovascular disease. Postprandial hyperlipidaemia has been investigated more recently in epidemiological, mechanistical and intervention studies, most of which indicate that high postprandial triglyceride levels, and particularly postprandial rich triglyceride remnants, constitute an increased risk for cardiovascular disease. Recent studies have shown that excessive postprandial glucose excursions are accompanied by oxidative stress and, less well known, activation of blood coagulation (increase in circulating D-dimers and prothrombin fragments). The mechanisms through which increased postprandial glucose levels and lipid concentrations may damage endothelial cells on blood vessel walls appear to be complex. These mechanisms include the activation of protein kinase C, increased expression of adhesion molecules, increased adhesion and uptake of leucocytes, increased production of proliferative substances such as endothelin, increased proliferation of endothelial cells, increased synthesis of collagen IV and fibronectin, and decreased production of nitric oxide (NO). In conclusion, the ‘postprandial state’ cumulatively covers almost half of the nycthemeral period, and its physiology involves numerous finely regulated motor, secretory, hormonal and metabolic events. Epidemiological and mechanistical studies have suggested that perturbations of the postprandial state are involved in cardiovascular disease. Correcting the abnormalities of the postprandial state must form part of the strategy for the prevention and management of cardiovascular diseases, particularly those that are associated with diabetes mellitus. Copyright © 1998 John Wiley & Sons, Ltd.

Coeliac disease in children and adolescents with IDDM: clinical characteristics and response to gluten-free diet.

Abstract: A total of 167 children and adolescents with insulin-dependent (Type 1) diabetes mellitus (97 males; age range 1.9-22.4 yrs) in a UK paediatric diabetic clinic were screened for coeliac disease using the IgA endomysial (EMA) test, or, in IgA deficient subjects, the IgG antigliadin (AGA) test. Antibody positive subjects were selected for small bowel biopsy, and confirmed coeliac cases started on a gluten free diet. Clinical features, height (Ht) standard deviation score (SDS), body mass index (BMI) SDS, HbA1c, insulin requirements' haemoglobin (Hb), mean red cell volume (MCV), serum folate and ferritin levels were evaluated at diagnosis and thereafter at 3-6 month intervals. A total of 156 subjects (93.4%) were antibody negative. Eleven (6.6%) were antibody positive (10 EMA/1 AGA; 6 males), of whom 9 had biopsies: 1 normal: 8 coeliac (4.8%; 5 males; 1 'classical'; 1 anaemia; 3 'atypical'; 3 asymptomatic). Seven coeliac subjects were followed during 12-24 months of dietary therapy. Pretreatment mean (range) Ht SDS = 0.08 (-1.66 to 1.88); BMI SDS = 0.32 (-0.82 to 1.29); HbA1c = 8.9 (6.2 to 11.3%); insulin dose = 0.98 (0.51 to 1.29) U kg(-1) day(-1). During treatment antibody status reverted to and remained negative, and symptoms resolved. By 24 months, there was a trend towards increased BMI SDS (mean (range) 1.31 (0.47 to 2.29), p = 0.248) and to reductions in HbA1c (8.1 (6.4-10.8), p = 0.697). Repeat small bowel biopsies were normal in 6 subjects (1 refused). No statistically significant changes occurred in any other parameters. In conclusion, serological screening is effective, although the therapeutic benefit of dietary therapy in asymptomatic cases remains uncertain.

Diabetes mellitus and female sexuality: a review of 25 years’ research

Abstract: Diabetes mellitus may cause debilitating somatic complications and a high psychosocial burden Impaired sexual function (erectile dysfunction) is a well-established complication in men Does diabetes also have an effect on sexuality of women? Since the first publication in 1971, only 15 studies in this area have been published and their results are contradictory The purpose of this article is to offer a review of these results As a conclusion, a new hypothesis on the specific influence of diabetes on female sexuality and suggestions for further research are formulated © 1998 John Wiley & Sons, Ltd

Comparison of prevalence and risk factors for microalbuminuria in South Asians and Europeans with Type 2 diabetes mellitus

Abstract: Although Type 2 (non-insulin-dependent) diabetes mellitus (Type 2 DM) is more common in South Asians than in Europeans in the UK, very little is known about complications and their risk factors in South Asians. We sought microalbuminuria in a cross-sectional study of 583 European and 889 South Asian Type 2 DM clinic attenders to Ealing Hospital, London, over 1 year. Albumin/creatinine ratios were measured in early morning urines. Prevalence of microalbuminuria was greater in South Asians compared to Europeans (40% versus 33% in men, p = 0.003, and 33% versus 19% in women, p < 0.0001). Glycaemic control was worse and prevalence of hypertension, retinopathy and heart disease was higher in South Asians. Key risk factors for microalbuminuria in both ethnic groups were glycaemic control, diabetes duration, blood pressure, triglyceride and retinopathy, but none accounted for the higher microalbuminuria prevalence in South Asians. Age and sex adjusted odds ratio for microalbuminuria was 1.78 (95% CI 1.02, 2.82, p = 0.02) in South Asians versus Europeans. After adjustment for confounders, this became 2.07, 95% CI 1.13, 3.79, p = 0.02. We conclude that microalbuminuria is more common in South Asians with Type 2 DM than in Europeans and, although risk factor relationships appeared similar in both groups, and some risk factors were more prominent in South Asians, this cannot account for the high prevalence of microalbuminuria observed in South Asians.

Long‐term effectiveness of a new α‐glucosidase inhibitor (BAY m1099‐miglitol) in insulin‐treated Type 2 diabetes mellitus

Abstract: In a double-blind, randomized study, miglitol (BAY m 1099), an α-glucosidase inhibitor, 100 mg tds or placebo was given orally with meals for a period of 24 weeks in 117 patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) treated with insulin. Fasting and 1 h postprandial plasma glucose and C-peptide were measured at the beginning and at the end of each 4-week interval and glycosylated haemoglobin was determined at day 0 and at the end of the 12th and 24th week. One hour postprandial plasma glucose was significantly lower in the miglitol group at the end of the 24th week (placebo: 11.6 ± 1.5 vs miglitol: 8.2 ± 1.5 mmol l−1, mean ± SD, p = 0.001). Diabetes control improved in the same group as the HbA1 was lowered by 16 % (p = <0.0001) at the end of the treatment. Mild reversible adverse effects were observed in 37 patients of the miglitol group (mainly flatulence and mild hypoglycaemia) and 2 of the placebo group. Urinary glucose was rendered negative in 41 patients in the miglitol group only. Thus miglitol appears to be a safe and effective adjunct in the management of Type 2 DM, in association with insulin. © 1998 John Wiley & Sons, Ltd.

Associations of body composition with type 2 diabetes mellitus

Abstract: The aims of this study were to establish the associations of stature, body mass index, waist to hip ratio, and waist circumference with Type 2 (non-insulin-dependent) diabetes mellitus in a random sample of 5887 men and 7018 women aged 20-59 years in a cross-sectional study set in The Netherlands. The crude prevalence of Type 2 diabetes (overall 1.58% in men, 0.94% in women) was significantly (p < 0.01) higher in shorter subjects and those with high body mass index, high waist to hip ratio, and larger waist circumference. Odds ratios and 95% confidence intervals (95% CI) were adjusted for age, cigarette smoking, alcohol consumption, physical activity, and education. Compared to the tallest tertile of height, odds ratios for Type 2 diabetes were 4.4 (95% CI: 1.3 to 11.5) in men and 1.6 (95% CI: 0.8 to 3.2) in women whose height was in the shortest tertile. Compared to the lowest tertile, odds ratios for Type 2 diabetes were 18.4 (95% CI: 4.3 to 78.5) in men and 5.3 (95% CI: 2.0 to 14.0) in women with waist to hip ratio in the highest tertile, 4.1 (95% CI: 2.0 to 8.4) in men and 2.1 (95% CI: 1.0 to 4.2) in women with body mass index in the highest tertile, and 4.9 (95% CI: 2.1 to 11.7) in men and 2.7 (95% CI: 1.2 to 5.9) in women with waist circumference in the highest tertile. In conclusion, although in longitudinal studies waist is a powerful predictor of diabetes incidence, Type 2 diabetes in a cross-sectional survey is associated with shortness in stature, as well as large waist circumference and high body mass index, and particularly strongly with high waist to hip ratio, suggesting that the development of Type 2 diabetes may modify hip circumference independently of body fat.

Prolonged and enhanced secretion of glucagon‐like peptide 1 (7‐36 amide) after oral sucrose due to α‐glucosidase inhibition (acarbose) in Type 2 diabetic patients

Abstract: GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and α-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects. In a cross-over study, 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP, glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates. With acarbose, sucrose reached the colon 60–90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1 increment 15 min after sucrose under both conditions, GLP-1 release was prolonged in the acarbose group (p = 0.001; significant from 210 to 360 min). Initially (0–150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p<0.001) were suppressed by acarbose, whereas later there were no significant differences. Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period (p = 0.02). We conclude that in hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1 release. © 1998 John Wiley & Sons, Ltd.

Screening for thyroid dysfunction in a community population of diabetic patients

Abstract: In a general practice population of 11,300 patients, 223 were known to have diabetes mellitus. Thirteen diabetic patients (5.8%) had a previous diagnosis of thyroid disease. The study excluded 17 patients who received sole diabetes care at a secondary referral centre (of whom 5 had a previous diagnosis of thyroid disease), 8 with a previous diagnosis of thyroid disease receiving community care, and 1 patient who declined screening. New thyroid disease was diagnosed in 11 patients (8 female, 3 male): 5 with primary hypothyroidism, 4 with subclinical hypothyroidism, 1 with hyperthyroidism and 1 with subclinical hyperthyroidism. Thus the prevalence of undiagnosed thyroid disease in diabetic patients receiving community diabetes care was 5.5% (9.5% of female patients), and the prevalence of thyroid disease (previously known and diagnosed as a result of screening) in the entire population of diabetic patients registered in the general practice was 10.8%. These findings suggest that screening for thyroid disease should be considered in patients receiving diabetes care in the community.

Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus.

Abstract: Gastrointestinal symptoms can be a limiting factor in optimizing metformin therapy, particularly at the onset of treatment. The underlying cause remains unclear. We have investigated whether metformin changes oral-caecal transit and if it causes bile salt malabsorption using the lactulose breath test and orally administered 14C-glycocholate followed by breath 14CO2 measurement over 6 h and stool collection for 72 h, respectively. Twenty-four diet and/or sulphonylurea treated patients underwent 7 days of baseline investigations before entering a randomized double-blind crossover study of 21 days duration with either metformin (850 mg bd) or placebo. No difference was observed in the oral-caecal transit time but a change in fasting plasma glucose was observed of 2.6 mmol l−1 (95 % CI 1.3, 3.8). Significant increases in percentage 14CO2 breath elimination were observed during treatment with metformin (9.7 ± 6.3) compared with placebo (3.1 ± 1.9) p = 0.020. In addition, percentage faecal 14C bile salt excretion was increased with metformin (17.2 ± 9.9 vs 10.1 ± 6.9) p = 0.037. A significant association (p = 0.002) emerged for stool bile salt content and liquidity of the stool. We conclude that metformin may cause gastrointestinal disturbances by reducing ileal bile salt reabsorption leading to elevated colonic bile salt concentrations. © 1998 John Wiley & Sons, Ltd.

Perceived symptoms of hypoglycaemia in elderly type 2 diabetic patients treated with insulin.

Abstract: Elderly insulin-treated diabetic patients have a high risk of severe hypoglycaemia, yet their hypoglycaemic symptom profile has attracted little research. In this study, the frequency and intensity of symptoms of hypoglycaemia were recorded using a validated questionnaire in 132 insulin-treated diabetic patients, aged 70 years or more. Principal components analysis (PCA) was used to discover the factorial structure of the symptoms. Lightheadedness and unsteadiness were prominent symptoms in the elderly patients. PCA suggested three separate groups of symptoms: (1) those related specifically to impairment of co-ordination and articulation; (2) more general neuroglycopenic symptoms, and (3) autonomic symptoms. The frequency and classification of hypoglycaemic symptoms in this elderly population is different from those seen in younger diabetic patients treated with insulin. Neurological symptoms of hypoglycaemia were more commonly reported and may be misinterpreted as features of cerebrovascular disease. Health professionals and carers involved in the treatment and education of diabetic patients should be aware of the age-specific differences in hypoglycaemic symptoms.

Randomized clinical trial of lifestyle interventions in Pima Indians: a pilot study

Abstract: A pilot trial was conducted to test adherence to specific lifestyle interventions among Pima Indians of Arizona, and to compare them for changes in risk factors for diabetes mellitus. Ninety-five obese, normoglycaemic men and women, aged 25-54 years, were randomized to treatments named 'Pima Action' (Action) and 'Pima Pride' (Pride), which were tested for 12 months. Action involved structured activity and nutrition interventions, and Pride included unstructured activities emphasizing Pima history and culture. Adherence to interventions, changes in self-reported activity and diet, and changes in weight, glucose concentrations, and other risk factors were assessed regularly. Thirty-five eligible subjects who had declined randomization were also followed as an 'observational' group and 22 members of this group were examined once at a median of 25 months for changes in weight and glucose concentration. After 12 months of intervention, members of both intervention groups reported increased levels of physical activity (median: Action 7.3 h month(-1), Pride 6.3 h month(-1), p < 0.001 for each), and Pride members reported decreased starch intake (28 g, p = 0.008). Body mass index, systolic and diastolic blood pressures, weight, 2-h glucose and 2-h insulin had all increased in Action members (p < 0.003 for each), and waist circumference had decreased in Pride members (p = 0.05). Action members gained more weight than Pride members (2.5 kg vs 0.8 kg, p = 0.06), and had a greater increase in 2-h glucose than Pride members (1.33 mM vs 0.03 mM, p = 0.007). Members of the observational group gained an average of 1.9 kg year(-1) in weight and had an increase of 0.36 mM year(-1) in 2-h glucose. Sustaining adherence in behavioural interventions over a long term was challenging. Pimas may find a less direct, less structured, and more participative intervention more acceptable than a direct and highly structured approach.

Diabetes mellitus in Egypt: glycaemic control and microvascular and neuropathic complications

Abstract: We performed a cross-sectional, population-based survey of persons 20 years of age and older living in Cairo and surrounding rural villages. The purpose was to describe glycaemic control and the prevalence of microvascular and neuropathic complications among Egyptians with diagnosed diabetes, previously undiagnosed diabetes, impaired glucose tolerance, and normal glucose tolerance. A total of 6052 households were surveyed. The response rate was 76% for the household survey and 72% for the medical examination. Among people with previously diagnosed diabetes, mean haemoglobin A1c, was 9.0%. Forty-two per cent had retinopathy, 21% albuminuria, and 22% neuropathy. Legal blindness was prevalent (5%) but clinical nephropathy (7%) and foot ulcers (1%) were uncommon in persons with diagnosed diabetes. Among people with diagnosed diabetes, microvascular and neuropathic complications were associated with hyperglycaemia. Retinopathy was also associated with duration of diabetes; albuminuria with hypertension and hypercholesterolaemia; and neuropathy with age, female sex, and hypercholesterolaemia. Albuminuria was as common in people with previously undiagnosed diabetes (22%) as those with diagnosed disease (21%). Mean haemoglobin A1c was lower (7.8%) and retinopathy (16%) and neuropathy (14%) were less prevalent in people with previously undiagnosed disease. Ocular conditions, blindness, and neuropathy were prevalent in the non-diabetic population. The microvascular and neuropathic complications of diabetes are a major clinical and public health problem in Egypt.

A low renal threshold for glucose in diabetic patients with a mutation in the hepatocyte nuclear factor-1α (HNF-1α) gene

Abstract: One form of maturity-onset diabetes of the young, Type 3 (MODY3), results from mutations in the gene coding for hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor first described in the liver. MODY3 is characterized by a defective glucose-stimulated insulin secretion. Earlier observations of glycosuria with normal blood glucose levels in some MODY families suggest an additional renal manifestation of the respective genetic defect. We measured the renal threshold for glucose in five diabetic carriers of a missense mutation (Arg 272 His) in HNF-1alpha and, for comparison, in eight Type 1 diabetic patients, applying a non-invasive protocol of frequent parallel blood and urine sampling during a slow shift in blood glucose levels. We found that the mean renal threshold for glucose was lowered in the HNF-1alpha diabetic patients compared to those with Type 1 diabetes (6.5 +/- 0.9 mmol l(-1) vs 10.7 +/- 0.5 mmol l(-1); p < 0.01). This lowered glucose threshold might be an indication of an extra-pancreatic effect of HNF-1alpha gene mutations in humans. Defects in HNF-1alpha may lead to an altered tubular glucose reabsorption, possibly due to decreased expression of the renal glucose transporter proteins involved in reabsorption of glucose from the urine.

Oral magnesium supplementation in insulin-requiring Type 2 diabetic patients.

Abstract: 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, HbA1c, 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; HbA1c: 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.

Lost to follow-up: the problem of defaulters from diabetes clinics.

Abstract: Diabetes mellitus requires lifelong self-management with regular health professional support and supervision. Estimates of the prevalence of failed appointments at diabetes clinics vary but at less than 10% appear to be lower than for other non-chronic conditions. Yet the patients who do not attend have significantly more risk factors and complications than those who keep their appointments. In addition, failed appointments reduce clinic efficiency. To date, research on non-attendance for health care has largely focused on the characteristics of defaulters and evaluation of simple interventions aimed at directly altering their appointment-keeping behaviour, such as mailed reminders. However, like the broader issue of adherence, there are many factors that predispose to non-attendance ranging from patient health beliefs and attitudes of health professionals, the organization of the clinic and the financial costs of attendance, to the degree of patient participation within consultations. Consequently, there is a range of strategies from patient reminders and induction videos, logistical and administrative changes in the clinic, to training in consultation skills for health professionals that have the potential to decrease the numbers of patients lost to follow-up. Whether these will reduce morbidity efficiently should be the subject of further work.

Sildenafil: study of a novel oral treatment for erectile dysfunction in diabetic men.

Abstract: The efficacy and safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, were evaluated in men with diabetes mellitus and erectile dysfunction (ED). Twenty-one men (aged 42-65 years) were enrolled in a double-blind, placebo-controlled, three-way crossover study conducted in two parts. In part I, the effect of a single dose (25 mg or 50 mg) of sildenafil or placebo on penile rigidity was assessed by penile plethysmography during visual sexual stimulation. In part II, daily diary records of erectile activity and a global efficacy question were used to evaluate once-daily dosing with 25 mg or 50 mg of sildenafil or placebo for 10 days. After a single 50 mg dose of sildenafil, the adjusted geometric mean duration (min) of penile rigidity >60% at the base of the penis during visual sexual stimulation was significantly increased (10.1 min) compared with placebo (2.8 min; p = 0.0053). In part II, sildenafil significantly increased the number of erections considered sufficiently hard for vaginal penetration compared with placebo (p = 0.0005). Improved erections were reported by 50% and 52% of patients treated with 25 mg and 50 mg of sildenafil, respectively, compared with 10% of those receiving placebo (p values < 0.05). Adverse events were mostly mild or moderate in nature and included muscular pains, headache, and dyspepsia. Sildenafil is a well-tolerated and potentially efficacious oral treatment for ED in men with diabetes mellitus.

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

Abstract: 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.