Quality of life in Type 1 (insulin-dependent) diabetic patients prior to and after pancreas and kidney transplantation in relation to organ function

Improvement of the quality of life in Type 1 (insulin-dependent) diabetic patients with severe late complications is one of the main goals of pancreas and/or kidney grafting. To assess the influences of these treatment modalities on the different aspects of the quality of life a cross-sectional study in 157 patients was conducted. They were categorized into patients pre-transplant without dialysis (n=29; Group A), pre-transplant under dialysis (n=44; Group B), post-transplant with pancreas and kidney functioning (n=31; Group C), post-transplant with functioning kidney, but insulin therapy (n=29; Group D), post-transplant under dialysis and insulin therapy again (n=15; Group E) and patients after single pancreas transplantation and rejection, with good renal function, but insulin therapy (n=9; Group F). All patients answered a mailed, self-administered questionnaire (217 questions) consisting of a broad spectrum of rehabilitation criteria. The results indicate a better quality of life in Groups C and D as compared to the other groups. In general the scores are highest in C, but without any significant difference to D. Impressive significant differences between C or D and the other groups were found especially in their satisfaction with physical capacity, leisure-time activities or the overall quality of life. The satisfaction with the latter is highest in C (mean±SEM: 4.0±0.2 on a 1 to 5-rating scale; significantly different from A: 3.1±0.1, B: 2.7±0.2 and E: 2.6±0.3; p<0.01), followed by D (3.8±0.2; significantly different from B and E; p<0.01). Group F shows a mean of 3.1±0.4, which is not significantly different from C. The percentages of patients in each group, who are not working: A: 38 %, B: 64 %, C: 74 %, D: 66 %, E: 87 % and F: 78 % indicate that there is no marked improvement in the vocational situation after successful grafting

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis