OBJECTIVE -Foot ulcers and their complications are an important cause of morbidity and mortality in diabetes. The present study aims to examine the long-term outcome in terms of amputations and mortality in patients with new-onset diabetic foot ulcers in subgroups stratified by etiology.RESEARCH DESIGN AND METHODS -Patients presenting with new ulcers (duration Ͻ1 month) to a dedicated diabetic foot clinic between 1994 and 1998 were studied. Outcomes were determined until March 2000 (or death) from podiatry, hospital, and district registers. Baseline clinical examination was done to classify ulcers as neuropathic, ischemic, or neuroischemic. Five-year amputation and mortality rates were derived from Kaplan-Meier survival analysis curves.RESULTS -Of the 185 patients studied, 41% had peripheral vascular disease (PVD) and 61% had neuropathy; 45%, 16%, and 24% of patients had neuropathic, ischemic, and neuroischemic ulcers, respectively. The mean follow-up period was 34 months (range 1-65) including survivors and patients who died during the study period. Five-year amputation rates were higher for ischemic (29%) and neuroischemic (25%) than neuropathic (11%) ulcers. Five-year mortality was 45%, 18%, and 55% for neuropathic, neuroischemic, and ischemic ulcers, respectively. Mortality was higher in ischemic ulcers than neuropathic ulcers. On multivariate regression analysis, only increasing age predicted shorter survival time.CONCLUSIONS -All types of diabetic foot ulcers are associated with high morbidity and mortality. The increased mortality appears to be independent of factors increasing ulcer riskthat is, neuropathy and PVD-in patients with established foot ulcers. Diabetes Care 26:491-494, 2003

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Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10−8) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10−9). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10−7), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Diabetes mellitus is an important and increasing cause of morbidity and mortality in sub-Saharan Africa. Accurate epidemiological studies are often logistically and financially difficult, but processes of rural-urban migration and epidemiological transition are certainly increasing the prevalence of type 2 diabetes. Type 1 disease is relatively rare, although this may be related to high mortality. This diabetic subgroup appears to present at a later age (by about a decade) than in Western countries. Variant forms of diabetes are also described in the continent; notably 'atypical, ketosis-prone' diabetes, and malnutrition-related diabetes mellitus. These types sometimes make the distinction between type 1 and type 2 diabetes difficult. Interestingly, this is also a current experience in the developed world. As more detailed and reliable complication studies emerge, it is increasingly apparent that African diabetes is associated with a high complication burden, which is both difficult to treat and prevent. More optimistically, a number of intervention studies and twinning projects are showing real benefits in varying locations. Future improvements depend on practical and sustainable support, coupled with local acceptance of diabetes as a major threat to the future health and quality of life of sub-Saharan Africans.

The suggestion of an increase in the number of sudden deaths of young people with Type 1 diabetes in the UK has been investigated. It was suggested that such deaths were due to hypoglycaemia and related to the increasing use of human insulin. In total we were notified of 50 deaths of people with Type 1 diabetes under age 50 years in the UK in 1989 which our informants (relatives, physicians, and pathologists) considered sudden and unexpected. An autopsy had been done in all cases and we supplemented this with detailed clinical information from relatives and case records. Of the 50 cases we excluded five with a definite cause of death, 11 suicides or self-poisonings, six cases of ketoacidosis, and four in which there was insufficient information about the circumstances of death to drawn any conclusions. Of the other 24 cases, two patients had been found with irreversible hypoglycaemic brain damage and died after a period of artificial ventilation. The most puzzling group were 22, aged 12-43 years, most of whom had gone to bed in apparently good health and been found dead in the morning. Nineteen of the 22 were sleeping alone at the time of death and 20 were found lying in an undisturbed bed. Most had uncomplicated diabetes and in none were anatomical lesions found at autopsy. There are major difficulties in diagnosing hypoglycaemia post-mortem, but the timing of death and other circumstantial evidence suggests that hypoglycaemia or a hypoglycaemia-associated event was responsible. All patients were taking human insulin at the time of death but most had been changed from animal insulin between 6 months and 2 years earlier and there was nothing to implicate the species of insulin as a factor in these deaths.

Severe hyponatraemia in hospital patients is associated with prolonged admissions and significantly increased mortality compared with normonatraemic patients. A particular group at high risk of death are those whose Na levels fall after admission. They may represent a 'sicker' group, and deserve increased monitoring and surveillance.

SummaryA survey of UK patients receiving the drug diazoxide, revealed 40 patients with insulinoma on this treatment. Mean age (±SD) was 67+18 years, and 74% were female. Duration of treatment was 7+6 years (range 1-22). Most (55%) patients were treated with diazoxide because of tumour non-localisation (including failed previous surgery). Metastatic disease (20%) and poor surgical risk (10%) were other indications. Side-effects (notably fluid retention and hirsutism) were common (47%) but not troublesome. Treatment was highly effective -59% were symptom free and 38% had only occasional symptoms. Only one patient had frequent hypoglycaemia despite treatment. We conclude that diazoxide is effective in the management of insulinoma. Side-effects are common but not problematic. Treatment should be considered for all patients not cured by surgery, or unsuitable for surgical treatment.

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