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Keep up with the latest research on diabetes

Diabetes mellitus is a condition characterised by raised blood sugar levels. In type 1 diabetes the pancreas fails to secrete insulin, and insulin is required to prevent death from ketoacidosis. Type 2 diabetes comes on slowly and is associated with both partial lack of insulin and insulin resistance. This type of diabetes is usually found in middle-aged or elderly patients and is a major health problem predicted to reach epidemic proportions by the year 2010. Obesity, hypertension, hypercholesterolaemia and hypertriglyceridaemia (the insulin-resistance syndrome) frequently accompany diabetes. Diabetes attacks both the small vessels, leading to blindness and renal failure, and the large vessels, leading to stroke, heart attack, gangrene and amputation.

This article highlights some of the recent studies into diabetes.

Repaglinide to treat type 2 diabetes
Repaglinide is a novel antidiabetic agent that has a rapid onset and short duration of action, and was developed for mealtime dosing. In a recently published study in Diabetes Care, a group of Danish researchers undertook a pharmacodynamic study to validate a prandial regimen of repaglinide by comparing meal-related dosing with a regimen in which the same total daily dose was divided into only two doses at morning and evening meals.

The study was a double-blind, randomised, parallel-group trial in 19 antidiabetic agent-naïve subjects with type 2 diabetes (mean age 58 years, known duration of diabetes 3.5 years, HbA1c 7.3%, and BMI 32). Patients were randomly assigned to receive repaglinide either before each of the three main meals or before breakfast and before the evening meal. Patients in both groups received the same total daily dose of repaglinide. Twenty-four-hour profiles of blood glucose, plasma insulin and plasma C-peptide concentrations were measured at baseline and after four weeks of treatment.

Repaglinide increased postprandial insulin levels and markedly reduced postprandial glucose levels relative to baseline in both groups. Significant reductions were also recorded in fasting blood glucose and HbA1c levels. The repaglinide regimen, in which a dose was taken before each main meal, was more effective in improving glycaemic control (including postprandial glucose and HbA1c levels) than the same total dose of repaglinide divided into morning and evening mealtime doses.
These results support the strategy of mealtime dosing with repaglinide. The improvements in glycaemic control observed in these patients are encouraging. In addition to classic parameters of glycaemic control, improvements in postprandial glucose excursions may prove to be important because postprandial hyperglycaemia has been suggested to be an independent risk factor for cardiovascular disease in diabetes.

Schmitz O, Lund S, Andersen PH, Jonler M, Porksen N. Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide. Diabetes Care 2002;25(2):342-6.

Control of blood sugar level reduces intensive care deaths
Serious illness and injury, as well as complicated surgical interventions, often require admission to an intensive care unit. In spite of all the advances in intensive care medicine – for example, artificial ventilation, high-tech heart and kidney functional support, and specialised (often costly) drugs – these illnesses cause many complications, such as serious infections and organ failure, which all greatly increase the risk of dying. There is about a 20% mortality rate among patients who depend on intensive care for longer periods. These patients also have high blood sugar levels, something that was until now regarded as the body’s way of coping with the stress induced by the illness.

A team of doctors and nurses from the University Hospital Gasthuisberg at KU Leuven, led by Prof Van den Berghe, carried out a study in which critically ill patients were given a special treatment with insulin to prevent elevated blood sugar levels. The study showed that, with this treatment, mortality rates were reduced to half. These results were published in the 8 November 2001 issue of the New England Journal of Medicine.

A total of 1,548 patients were involved in the study. When admitted to the intensive care unit, the patients were divided at random into two groups. One group underwent their treatment that is standard for intensive care units worldwide: they were administered insulin only when the blood sugar level exceeded 215mg/dl. The other group of patients was given an intensive insulin treatment with the aim of maintaining blood sugar levels at a perfectly normal level (0–110mg/dl). All other medical and nursing care was guaranteed for both groups.

The intensive insulin treatment reduced mortality by 42%. This is attributed primarily to the reduced frequency of complications such as serious infections, organ failure (eg, kidney failure), generalised nerve damage and muscle weakness. As a consequence, there is less need for specialised and expensive treatments such as long-term antibiotic use, ­dialysis or other types of renal replacement therapies, blood transfusions and prolonged artificial ventilation. The result is that patients can be more quickly discharged from intensive care.

The upshot from this study is threefold:

  1. This is good news for patients. The application of this new treatment increases the chance of ­survival. In concrete terms, it means that with this treatment an average of four fewer patients will die each month in the intensive care unit at the University Hospital Leuven. If applied in every intensive care unit in the Western world, it would mean that several thousand lives per month could be saved. Looking back on several decades of intensive care medicine, only the introduction of artificial ventilation has produced comparable results.
  2. This treatment is good news for hospitals. The lifesaving effects are also cost-effective, as it reduces the need for more costly treatments and reduces time spent in intensive care.
  3. This study is significant from a scientific point of view. It demonstrates the deleterious effect of high blood sugar levels, even when the patient does not suffer from diabetes. Further research will be needed to find out what the underlying mechanisms are. Future studies will also need to examine whether these results can be applied to other acute and chronic illnesses. The study already confirms that close monitoring of blood sugar levels in diabetics can prevent significant complications.

Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the surgical intensive care unit. N Engl J Med 2001;345(19):1359-67.

Diabetes treatment may be a risk factor for acute pancreatitis
Researchers from the Karolinska Institute in Sweden have been evaluating risk factors, notably drugs, for acute pancreatitis.

A population-based case-control study was conducted of 1.4 million inhabitants, aged 20–85 years, from four regions in Sweden between 1 January 1995 and 31 May 1998. A total of 462 case subjects were hospitalised in surgery departments for their first episode of acute pancreatitis without previous gallbladder disease. A total of 1,781 control subjects were randomly selected from a population register. Information was obtained from case records and through telephone interviews.

A total of 27 case subjects (6%) and 55 control subjects (3%) had prevalent diabetes. A total of 53 case subjects (11%) and 130 control subjects (7%) had a BMI >30. Use of glyburide had a crude odds ratio (OR) of 3.2, and in a multivariate logistic regression adjusted for covariates the OR for use of glyburide was 2.5. BMI had a continuous OR of 1.2 per five units of BMI. The relative risk for hospitalisation longer than 14 days or treatment in an intensive care unit was 2.4 among patients with a BMI >30 when compared with patients with a BMI between 20 and 25.

Use of glyburide and obesity may both be risk factors for acute pancreatitis. Obesity is associated with an extended hospitalisation time in subjects with acute pancreatitis.

Blomgren KB, Sundstrom A, Steineck G, Wiholm BE. Obesity and treatment of diabetes with glyburide may both be risk factors for acute pancreatitis. Diabetes Care 2002;25(2):298-302.

Erectile dysfunction in type 2 diabetic patients
Within the context of a large, nationwide outcomes research programme in type 2 diabetes, the prevalence of self-reported erectile dysfunction was assessed and its impact on quality of life evaluated.

The study involved 1,460 patients enrolled by 114 diabetes outpatient clinics and 112 general practitioners. Patients were asked to complete a questionnaire investigating their ability to achieve and maintain an erection. Various aspects of quality of life were also assessed depressive using the following instruments: SF-36 Health Survey, diabetes health distress, psychological adaptation to diabetes, depressive symptoms (CES-D scale) and quality of sexual life.

Overall, 34% of the patients reported frequent erectile problems, 24% reported occasional problems and 42% reported no erectile problems. After adjusting for patient characteristics, erectile dysfunction was associated with higher levels of diabetes-specific health distress and a poor psychological adaptation to diabetes, which were in turn related to worse metabolic control. Erectile problems were also associated with a dramatic increase in the prevalence of severe depressive symptoms, lower scores in the mental components of the SF-36, and a less satisfactory sexual life. A total of 63% of the patients reported that their physicians had never investigated their sexual problems.

Erectile dysfunction is extremely common among type 2 diabetic patients and is associated with poorer quality of life, as measured with generic and diabetes-specific instruments. Despite their relevance, sexual problems are seldom investigated by general practitioners and specialists.

De Berardis G, Franciosi M, Belfiglio M, et al. Erectile dysfunction and quality of life in type 2 diabetic patients: a serious problem too often overlooked. Diabetes Care 2002;25(2):284-91

Smoking in pregnancy linked to diabetes and obesity
Researchers from Sweden have showed that smoking during pregnancy increases the risk of the child developing diabetes and obesity in later life. They also showed that cigarette smoking as a young adult is associated with an increased risk of subsequent diabetes.

The authors used British data on about 17,000 births from 3 to 9 March 1958. At birth, midwives recorded information on smoking during pregnancy (after the 4th month). Details of maternal smoking were again recorded in 1974. The group’s own smoking behaviour was recorded during an interview at age 16.

Medical examinations and record reviews were conducted at ages seven and 16 years, and a personal interview at age 33 years asked about diabetes. Among those followed fully throughout childhood and adolescence to age 33, 15 men and 13 women were identified who had developed diabetes between 16 and 33 years, and 602 individuals (10%) were obese at age 33.

The association of diabetes with maternal smoking specifically during pregnancy suggests that it is a risk factor for early adult onset diabetes, say the authors. Cigarette smoking as a young adult was also independently associated with an increased risk of subsequent diabetes. Study members without diabetes, but whose mothers smoked during pregnancy, were significantly more likely to be obese or overweight by age 33 years.

They suggest that in-utero exposure to smoking results in lifelong metabolic dysregulation, possibly due to fetal malnutrition or toxicity, and stress that smoking during pregnancy should always be strongly discouraged.

Montgomery S, Ekbom A. Smoking during pregnancy and diabetes mellitus in a British longitudinal birth cohort. BMJ 2002;324:26-7.

European Association of Diabetes (EASD)
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European Foundation for the Study of Diabetes (EFSD)
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