Post-transplantation diabetes is better controlled after conversion from prednisone to deflazacort: a prospective trial in renal transplants

It is well known that long-term use of steroids plays a decisive role in the development of glucose intolerance and diabetes mellitus (DM). Deflazacort, an oxazoline derivative of prednisolone, has been introduced as a potential substitute for conventional steroids in order to ameliorate glucose intolerance. We initiated a randomized study of conversion from prednisone to deflazacort in kidney transplantation (Tx) recipients presenting with pre-Tx or post-Tx DM to ascertain whether or not the switch to deflazacort would ameliorate the diabetic state. Forty-two recipients in the conversion group were compared with 40 patients on prednisone (the control group) in a prospective manner. The dose reduction of insulin or oral blood glucose-lowering agents, the adequacy of glucose control, and the development of side effects were the criteria for evaluating outcome. In the conversion group, patients were switched to deflazacort at a dose ratio of 6 mg deflazacort to 5 mg prednisone. During the mean follow-up period of 13.2 months, neither graft dysfunction nor acute rejection developed in the conversion group. Improvement in blood glucose control in the conversion group was noted. When the conversion group was stratified into pre- or post-Tx DM, promising effects were clearly evident in the post-Tx DM patients. More than 50 % dose reduction of blood glucose-lowering agents was possible in 42.3 % of post-Tx DM patients. In conclusion, it was readily possible to control blood glucose better in post-Tx DM recipients without seriously affecting the immunosuppressive activity after conversion to deflazacort. Received: 20 August 1996 Received after revision: 25 November 1996 Accepted: 6 December 1996     

Therapeutic traditions in type 2 diabetes — are they changing?

The utilisation of antidiabetic drugs reflects both the prevalence of diabetes and the different therapeutic traditions of physicians. A questionnaire survey to study attitudes to the use of oral antidiabetic drugs amongst physicians and possible changes in treatment habits was carried out in a representative sample of Finnish physicians (n=454) in 1992 and the results were compared with those of a similar survey carried out in 1985, and with drug utilisation statistics.The mean fasting blood glucose level at which a physician would start pharmacological treatment was 8.7 mmol·l^–1, which was significantly lower than in the 1985 survey. The responses to various case histories suggested a more active approach to pharmacological treatment compared to the 1985 survey. Insulin treatment especially seems to have gained in popularity. This change in attitude was paralled by an increase in the consumption of antidiabetic drugs in Finland during the observation period. The increase in use of oral drugs was steeper in Finland than in Norway and Sweden.Whether this active approach will improve the metabolic control and prognosis of patients with Type 2 diabetes, remains to be demonstrated.     

Does the Prepubertal Duration of Diabetes Influence the Onset of Microvascular Complications?

This study investigated the relationship between the development of diabetic retinopathy and pubertal status at onset of diabetes in 521 Type 1 diabetic patients diagnosed between 1950 and 1985. Pubertal status was based on age at onset (girls ≧ 11 years and boys ≧ 12 years). Retinopathy (all forms) developed in 112 patients (21.5%; 65 background and 47 proliferative retinopathy). For subjects diagnosed in either the prepubertal or postpuberal period, a similar proportion survived without developing retinopathy for any given duration of diabetes (X² = 0.3822, p = 0.54). However, if only the postpubertal duration of diabetes is considered, then the proportion of patients surviving without retinopathy was significantly less for those diagnosed in the prepubertal period (X² = 14.2, p = 0.002). This study suggests that the prepubertal duration of diabetes is an important phase and that the years prior to puberty do contribute to the risk of developing microvascular injury.     

A survey of the use of special food products by diabetics

A food frequency of consumption questionnaire was completed by 137 diabetic outpatients attending the University of Wales Hospital in Cardiff, to provide information about the use of special dietary products.
Seventy-four per cent of the diabetics used special dietary products, the most popular of which were artificial sweeteners (45%) and preserves (47%), followed by squash (34%), sweets (31%) and chocolate (31%). Twenty per cent of diabetics consumed biscuits and tinned fruit. Cake and other products (e.g. jelly), were used by less than 10% of the respondents. Over half of all the diabetics consumed one or more products on a daily basis. The use of special products bore no significant relationship to the sex of the respondents, nor to the duration of the diabetes. However, a significantly higher proportion of the Insulin Dependent Diabetics (IDDM) group used dietary products compared with the Non-Insulin Dependent Diabetics (NIDDM) group. This can be explained largely by the differences in age between the diabetics; the under-18-year-old age group (who were all IDDM respondents) were the greatest users of sweets, chocolate and squash.
Forty-three per cent of diabetics who did not use special food products cited at least one reason for non-use. The reasons included dietetic advice (NIDDM respondents only), high cost, poor palatability, lack of availability and unsuitability for other members of the family.     

Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function--the DICOF trial.

BACKGROUND: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management. AIM: To evaluate structured TTP for geriatric patients with impaired cognitive function. PATIENTS AND METHODS: A neuropsychological examination was performed on all patients over 54 years [n=102, age 68.6 +/- 8.7 years, diabetes duration 10.3 (0.03-35.4) years, HbA1c 10.3 +/- 1.7% (HPLC, Diamat, NR 4.5-6.3%), cognitive function 87.7 +/- 12.3 IQ points] who took part in TTP for insulin therapy. Patients with impaired cognitive function participated either in the standard TTP of Berger [n = 35, age 67.6 +/- 8.9 years, diabetes duration 9.9 (0.04-35.4) years, HbA1c 10.3 +/- 2.0%] or in the specialized structured geriatric DICOF-TTP [n=33, age 70.4 +/- 8.2 years, diabetes duration 10.4 (0.03-24.9) years, HbA1c 10.7 +/- 1.8%]. RESULTS: After TTP there were no differences in knowledge and ability for diabetes self-management (standard/DICOF: knowledge 11.0 +/- 2.6 vs. 12.2 +/- 2.7 points, P = 0.11; handling 14.9 +/- 3.3 vs. 15.9 +/- 2.5 points, P = 0.18). However, patients who took part in the DICOF programme showed better scores in satisfaction with the education programme [standard/DICOF 44.7 (31-57) vs. 52.5 (45-59) points, P < 0.001]. Six months later the DICOF participants showed better results regarding diabetes self-management (standard/DICOF: handling 12.5 +/- 4.1 vs. 15.9 +/- 3.1 points, P = 0.001). Both groups showed HbA1c decrease (8.3 +/- 1.4 vs. 8.5 +/- 1.3%, P=0.62) and similar incidence of acute complications. CONCLUSIONS: Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management.     

100例2型糖尿病患者交感神经皮肤反应研究

目的探讨交感神经皮肤反应(SSR)检测在评价2型糖尿病(T2DM)自主神经损害中的价值.方法对100例T2DM患者进行SSR检测,30例健康志愿者作为对照.结果2组SSR的起始潜伏期、N波潜伏期、波幅、面积比较差异有显著性意义(P＜0.05),P波潜伏期差异无显著性意义(P＞0.05).T2DM组72例(72%)患者至少有一肢SSR异常.血糖控制满意组和血糖控制不良组比较,起始和N波潜伏期差异有统计学意义(P＜0.05),波幅和面积无显著性意义(P＞0.05).T2DM组病程＜5年与病程≥5年比较,潜伏期、波幅、面积差异均无统计学意义(P＞0.05).结论SSR可作为评价T2DM自主神经损害的客观电生理指标;T2DM患者SSR与血糖控制水平相关,与病程无关.     

Evaluating risk factors associated with severe hypoglycaemia in epidemiology studies—what method should we use?

AIMS: To determine the most appropriate regression models to use when assessing risk factors for severe hypoglycaemia and to investigate the impact of model misspecification and its clinical implications. METHODS: A total of 1229 children with Type 1 diabetes (mean age 11.7 years sd 4.1), of which 605 (49.2%) were males, were studied. Prospective assessment of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was made over the 9-year period, 1992-2001. Patients were seen every 3 months and episodes of hypoglycaemia along with clinical data were recorded. Over 70% of children never experienced a severe hypoglycaemic event. Data were analysed using the Poisson regression, negative binomial, zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models. The over-dispersion and likelihood ratio statistics were calculated and the analytical methods compared. RESULTS: The Poisson regression model did not fit the data well. The negative binomial and the zero inflated Poisson and negative binomial models fitted the data better than Poisson. CONCLUSIONS: The commonly used Poisson regression models to analyse hypoglycaemia epidemiology may lead to biased parameter estimates and incorrect determination of risk factors for hypoglycaemia. We recommend the use of the negative binomial or zero inflated models to examine any risk factors associated with severe hypoglycaemia. Careful consideration must be given to the interpretation of hypoglycaemia surveys and their analysis.     

Evidence for a Type 1 diabetes‐specific mechanism for the insulin gene‐associated IDDM2 locus rather than a general influence on autoimmunity

Aims The Type 1 diabetes susceptibility locus, IDDM2, has been mapped to a variable number of tandem repeats (VNTR) region 5′ upstream of the insulin (INS) and insulin‐like growth factor (IGF2) genes on chromosome 11p15. The function of the VNTR is uncertain; however, it may influence the thymic expression of the insulin gene and affect the development of immune self‐tolerance. The aim of this study was to investigate whether the INS VNTR region is a Type 1 diabetes‐specific locus or acting as a general autoimmunity gene. Methods We genotyped the INS‐IGF2 VNTR [using the surrogate INS?23 HphI single nucleotide polymorphism (SNP)] in 823 Graves’ disease (GD)/multiple sclerosis (MS) families, 1433 GD/MS patients and 837 healthy control subjects. Results We found no evidence of excess transmission of the allele associated with Type 1 diabetes to individuals affected by GD or MS within the families. Analysis of the case–control dataset showed no genotypic or allelic difference between the two populations. Conclusions These data suggest that the INS‐IGF2 VNTR is acting as a Type 1 diabetes‐specific susceptibility gene rather than as an influence on general autoimmunity.     

Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren repository.

AIMS: Autoimmune disorders co-exist in the same individuals and in families, implying a shared aetiology. The aim of this study was to compare the prevalence of the common autoimmune diseases in the parents of siblings from the Type 1 diabetes Warren repository with the general population. METHODS: Between 1989 and 1996, 505 British families with at least two siblings affected by Type 1 diabetes were recruited. Clinical information was collected regarding the presence of autoimmune disease in the parents and the prevalence of disease in the parents was compared with that expected in the general population. RESULTS: The prevalence of autoimmune disease in the parents was significantly higher in the repository compared with that expected in the general population [P-value = 1.98 x 10(-5) (female), P-value = 1.1 x 10(-8) (male)]. Type 1 diabetes was recorded in 63/1010 (6.2%) parents with a marked paternal preponderance (9.5 vs. 3%P = 0.002). Other autoimmune diseases affected 27% of parents with diabetes and 13.2% of parents without diabetes (P < 0.01). CONCLUSION: These data confirm the importance of family history as a significant risk factor for the development of Type 1 diabetes and support the hypothesis that the common autoimmune diseases share at least some aetiological mechanisms.     

Regulation of β-cell mass and function by the Akt/protein kinase B signalling pathway

The insulin receptor substrate-2/phosphoinositide 3-kinase (PI3K) pathway plays a critical role in the regulation of β-cell mass and function, demonstrated both in vitro and in vivo . The serine threonine kinase Akt is one of the promising downstream molecules of this pathway that has been identified as a potential target to regulate function and induce proliferation and survival of β cells. Here we summarize some of the molecular mechanisms, downstream signalling pathways and critical components involved in the regulation of β-cell mass and function by Akt.