Tahseen A Chowdhury

Association of apolipoprotein ε2 allele with diabetic nephropathy in Caucasian subjects with IDDM

Epidemiological and family studies imply that genetic factors are important in the etiology of diabetic nephropathy in subjects with IDDM (1,2). Vascular disease is characteristic of nephropathy, and lipoproteins are important determinants of atherosclerosis. Apolipoprotein E (apoE) is a major protein constituent of lipoproteins, mediating hepatic lipoprotein uptake and reverse cholesterol transport. ApoE occurs as three isoproteins: E3 with normal function, E2 with reduced affinity, and E4 with increased affinity for the apoE receptor. These are encoded by three codominant alleles e2, E3, and e4. This polymorphism has an influence on lipid levels, the E2 isoform being associated with lower cholesterol but higher triglyceride levels compared with the E3 isoform, and the E4 isoform being associated with higher cholesterol but lower triglyceride levels (3). There is also an association with vascular disease in diabetic and nondiabetic populations (3,4). Preliminary data suggest that this triallelic polymorphism may be associated with genetic susceptibility to diabetic nephropathy (5). The aim of this study was thus to determine the role of the apoE gene polymorphism in a large cohort of IDDM patients with and without diabetic nephropathy. Four patient cohorts were examined: IDDM patients with diabetic nephropathy (nephropathy group, n = 252), IDDM patients with long duration of disease and no nephropathy (long-duration non-nephropathy group [LDNN], n = 197), a

Management of people with diabetes wanting to fast during Ramadan.

#### Summary points The holy month of Ramadan is one of five main pillars of being a Muslim. Most Muslims are passionate about fasting during this month. Although the Koran exempts sick people from the duty of fasting,1 2 many Muslims with diabetes may not perceive themselves as sick and are keen to fast. A large epidemiological study of Muslims with diabetes in 13 Muslim countries (n=12 914)—the EPIDIAR study—showed that 43% of patients with type 1 and 79% of those with type 2 diabetes fasted during Ramadan.3 As the month of Ramadan follows the lunar calendar, the fasting month is brought forward by about 10 days each year, which means that over time the season in which Ramadan falls changes. For the next decade Ramadan will fall in the summer in the northern hemisphere. As daylight hours vary considerably between summer and winter months in non-equatorial countries, the length of the fast (which lasts from dawn to sunset) increases in the summer (to about 16-20 hours). People with diabetes who fast are at risk of adverse events, and the risks may increase with longer fasting periods. We review the evidence for optimum management of diabetic patients who wish to fast …

Preventing diabetes in south Asians

Too little action and too late The south Asian diaspora in the United Kingdom comprises Indians (predominantly Gujaratis and Punjabis), Sri Lankans, Pakistanis, and Bangladeshis. A dramatic increase in the prevalence of type 2 diabetes in south Asians is observed in many parts of the world including the United Kingdom.1 While marked cultural and social differences arise within this racial group, south Asians have the unenviable distinction of achieving the highest death rates of coronary heart disease in the United Kingdom,2 with Bangladeshis being particularly disadvantaged.3 Much of this excess risk may be attributed to the increased risk of type 2 diabetes (four times that of Europeans), which develops about 10 years earlier than in Europeans,4 and renal and cardiac complications are encountered more commonly.5 Although genetic factors are important, the increased incidence of type 2 diabetes is strongly associated with increasing central (intra-abdominal) obesity and hyperinsulinaemia.6 South Asians seem to be more insulin resistant, even at an early age.7 The relation between obesity and insulin resistance may occur at lower levels of …

Poor glycaemic control caused by insulin induced lipohypertrophy

Good glycaemic control reduces the risk of complications of diabetes.1 Secondary failure of oral hypoglycaemic treatment is common in patients with type 2 diabetes, and thus insulin treatment is often needed to improve glycaemic control. Indeed, in the UK prospective diabetes study 38% of patients with type 2 diabetes needed insulin treatment after 10 years.1 The reasons for poor glycaemic control are many; and despite insulin treatment many patients with diabetes have poor glycaemic control.2 Lipohypertrophy is characterised by a benign “tumour-like” swelling of fatty tissue secondary to subcutaneous insulin injections. We describe two cases in which poor glycaemic control was directly related to insulin induced lipohypertrophy, recognition of which led to major improvements in glycaemic control. ### Case 1 A 37 year old woman had been given a diagnosis of type 1 diabetes when she was 7 years old. She was treated with soluble insulin twice daily. She was transferred to our diabetes unit in 2000. She had experienced problems with fluctuating blood glucose concentrations, recurrent hyperglycaemia, and frequent unpredictable hypoglycaemia, despite compliance with diet and regular self monitoring of blood glucose. At her most recent annual review she was noted to have mild background retinopathy but no other microvascular or macrovascular complications of diabetes. Results of lipid, urea and electrolytes, and thyroid function tests were normal, but her glycated haemoglobin was 9.1% (normal range 3.6% to 5.1%). She was treated with Human Actrapid (Novo Nordisk) at a …

Diabetes and Cancer

Diabetes and cancer are common conditions, and their co-diagnosis in the same individual is not infrequent. A link between the two conditions has been postulated for almost 80 years, but only in the past decade has significant epidemiological evidence been amassed to suggest that diabetes and cancer are associated, and the link appears causal. Hyperinsulinaemia, adipocytokines, growth factors and epigenetic changes may be implicated in the pathogenesis of cancer amongst patients with diabetes, and recently, diabetes therapies have also been implicated. There is reasonable circumstantial evidence that metformin may decrease the risk of cancer amongst diabetic patients. Much more research is required to elucidate the link between diabetes and cancer, particularly the potential link with diabetes treatments.

Prevalence and reasons for insulin refusal in Bangladeshi patients with poorly controlled Type 2 diabetes in East London.

Aims  To determine the prevalence and reasons for refusal to commence insulin in Bangladeshi patients with Type 2 diabetes.

Lack of association of angiotensin II type 1 receptor gene polymorphism with diabetic nephropathy in insulin-dependent diabetes mellitus.

Several observations suggest that inherited factors are influential in the development of nephropathy in patients with insulin‐dependent diabetes mellitus (IDDM). Genetic components of the renin angiotensin system are possible candidate genes. The aim of this study was to determine the role of the hypertension associated angiotensin II type 1 receptor (AT1R) gene A1166C polymorphism in susceptibility to nephropathy in IDDM. We examined 264 Caucasoid patients with IDDM and overt nephropathy (as defined by persistent proteinuria in the absence of other causes, hypertension and retinopathy), 136 IDDM patients with long duration of diabetes and no nephropathy (LDNN group), 200 recently diagnosed IDDM patients (Sporadic Diabetic group), and 212 non‐diabetic subjects. The AT1R gene polymorphism was assessed using the polymerase chain reaction and restriction isotyping. Genotype frequencies did not differ significantly between the sporadic diabetic group and the nephropathy group (p = 0.245), nor between the long duration non‐nephropathy group and the nephropathy group (p = 0.250). Allele frequencies were not significantly different between the three groups (p = 0.753). We conclude that there is no significant association between the hypertension associated AT1R gene polymorphism and diabetic nephropathy in patients with IDDM in the UK.

Managing diabetes in dialysis patients

Burgeoning levels of diabetes are a major concern for dialysis services, as diabetes is now the most common cause of end-stage renal disease in most developed nations. With the rapid rise in diabetes prevalence in developing countries, the burden of end stage renal failure due to diabetes is also expected to rise in such countries. Diabetic patients on dialysis have a high burden of morbidity and mortality, particularly from cardiovascular disease, and a higher societal and economic cost compared to non-diabetic subjects on dialysis. Tight glycaemic and blood pressure control in diabetic patients has an important impact in reducing risk of progression to end stage renal disease. The evidence for improving glycaemic control in patients on dialysis having an impact on mortality or morbidity is sparse. Indeed, many factors make improving glycaemic control in patients on dialysis very challenging, including therapeutic difficulties with hypoglycaemic agents, monitoring difficulties, dialysis strategies that exacerbate hyperglycaemia or hypoglycaemia, and possibly a degree of therapeutic nihilism or inertia on the part of clinical diabetologists and nephrologists. Standard drug therapy for hyperglycaemia (eg, metformin) is clearly not possible in patients on dialysis. Thus, sulphonylureas and insulin have been the mainstay of treatment. Newer therapies for hyperglycaemia, such as gliptins and glucagon-like peptide-1 analogues have become available, but until recently, renal failure has precluded their use. Newer gliptins, however, are now licensed for use in ‘severe renal failure’, although they have yet to be trialled in dialysis patients. Diabetic patients on dialysis have special needs, as they have a much greater burden of complications (cardiac, retinal and foot). They may be best managed in a multidisciplinary diabetic–renal clinic setting, using the skills of diabetologists, nephrologists, clinical nurse specialists in nephrology and diabetes, along with dietitians and podiatrists.

Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double-blind placebo-controlled trial.

To investigate the effect of short‐term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes.

Improving outcomes for patients with type 2 diabetes using general practice networks: a quality improvement project in east London

Background Structured diabetes care can improve outcomes and reduce risk of complications, but improving care in a deprived, ethnically diverse area can prove challenging. This report evaluates a system change to enhance diabetes care delivery in a primary care setting. Methods All 35 practices in one inner London Primary Care Trust were geographically grouped into eight networks of four to five practices, each supported by a network manager, clerical staff and an educational budget. A multidisciplinary team developed a ‘care package’ for type 2 diabetes management, with financial incentives based on network achievement of targets. Monthly electronic performance dashboards enabled networks to track and improve performance. Network multidisciplinary team meetings including the diabetic specialist team supported case management and education. Key measures for improvement included the number of diabetes care plans completed, proportion of patients attending for digital retinal screen and proportions of patients achieving a number of biomedical indices (blood pressure, cholesterol, glycated haemoglobin). Results Between 2009 and 2012, completed care plans rose from 10% to 88%. The proportion of patients attending for digital retinal screen rose from 72% to 82.8%. The proportion of patients achieving a combination of blood pressure ≤140/80 mm Hg and cholesterol ≤4 mmol/L rose from 35.3% to 46.1%. Mean glycated haemoglobin dropped from 7.80% to 7.66% (62–60 mmol/mol). Conclusions Investment of financial, organisational and education resources into primary care practice networks can achieve clinically important improvements in diabetes care in deprived, ethnically diverse communities. This success is predicated on collaborative working between practices, purposively designed high-quality information on network performance and engagement between primary and secondary care clinicians.