Sharon Kozak

Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy.

Background. The effect of islet cell transplantation (ICT) on the progression of diabetic microvascular complications is not well understood. Methods. We have conducted a prospective, crossover, cohort study comparing ICT with intensive medical therapy on the progression of diabetic nephropathy, retinopathy, and neuropathy. Results. The rate of decline in glomerular filtration rate is slower after ICT than on medical therapy. There was significantly more progression of retinopathy in medically treated patients than post-ICT. There was a nonsignificant trend for improved nerve conduction velocity post-ICT. Conclusions. ICT is associated with less progression of microvascular complications than intensive medical therapy. Multicenter, randomized trials are needed to further study the role of ICT in slowing the progression of diabetic complications.

A multi-year analysis of islet transplantation compared with intensive medical therapy on progression of complications in type 1 diabetes.

Background. We hypothesized that transplantation of islets into type 1 diabetics could improve outcomes of glucose metabolism, renal function, retinopathy, and neuropathy compared with intensive medical therapy. Methods. We conducted a prospective, crossover, cohort study of intensive medical therapy (group 1) versus islet cell transplantation (group 2) in 42 patients. All were enrolled in group 1 then 31 crossed over with group 2 when islet donation became available. Transplantation was performed by portal venous embolization of more than 12,000 islet equivalents/kg body weight under cover of immunosuppression with antithymocyte globulin, tacrolimus, and mycophenolate. Outcome measures were HbA1c, change in glomerular filtration rate (GFR), progression of retinopathy, and change in nerve conduction velocity. This report details interim analysis of outcomes after 34±18 months (group 1) and 38±18 months (group 2). Results. HbA1c (%) in group 1 was 7.5±0.9 versus 6.6±0.7 in group 2 (P<0.01). GFR (mL/min/month) declined in both groups (group 1 −0.45±0.7 vs. group 2 −0.12±0.7, P=0.1). Slope of the GFR decline in group 1 was significantly more than 0. Retinopathy progressed in 10 of 82 eyes in group 1 versus 0 of 51 in group 2 (P<0.01). Nerve conduction velocity (m/sec) remained stable in group 1 (47.8±5 to 47.1±5 m/sec) and group 2 (47.2±4.5 to 47.7±3.5). Conclusion. Islet transplantation yields improved HbA1c and less progression of retinopathy compared with intensive medical therapy during 3 years follow-up.

The effect of medical therapy and islet cell transplantation on diabetic nephropathy : An interim report

Background. The effect of islet cell transplantation (ICT) on renal function in type 1 diabetes is uncertain and some recent studies report a significant decline in estimated glomerular filtration rate (GFR) and worsening of albuminuria. Methods. We are conducting a prospective crossover study comparing medical treatment with islet transplantation on the progression of diabetic complications, including renal function. The primary endpoint is change in GFR measured by 99mTc-diethylenetriaminepentaacetate with secondary endpoints including estimated GFR and albumin excretion. Results. We have followed 21 patients after islet transplantation a median of 29 months (range 13–45) and compared their results with medically treated patients followed a median 29.5 months (range 13–56). There is no difference in the rate of decline in measured GFR between medically treated patients (–0.35±0.89; 95% CI: –0.57 to –0.13 mL/min/month/1.73 m2) and those after ICT (–0.31±1.18; 95% CI: –0.61 to –0.01) and neither is significantly different from that expected for the general population. The rate of decline in our estimated GFR results is lower than that reported in other studies and we did not find any worsening of albuminuria. Conclusions. We do not find evidence of worsening of renal function after islet transplantation compared with medically treated patients.

Reduced progression of diabetic retinopathy after islet cell transplantation compared with intensive medical therapy.

Background. Diabetic retinopathy is a major complication of type 1 diabetes and remains a leading cause of visual loss. There have been no comparisons of the effectiveness of intensive medical therapy and islet cell transplantation on preventing progression of diabetic retinopathy. Methods. The British Columbia islet transplant program is conducting a prospective, crossover study comparing medical therapy and islet cell transplantation on the progression of diabetic retinopathy. Progression was defined as the need for laser treatment or a one step worsening along the international disease severity scale. An interim data analysis was performed after a mean 36-month follow-up postislet transplantation and these results are presented. Results. The medical and postislet transplant groups were similar at baseline. Subjects after islet transplantation had better glucose control than the medically treated subjects (mean HbA1c 6.7%±0.9% vs. 7.5±1.2, P<0.01) and were C-peptide positive. Progression occurred significantly more often in all subjects in the medical group (10/82 eyes, 12.2%) than after islet transplantation (0/51 eyes, 0%) (P<0.01). Considering only subjects who have received transplants, progression occurred in 6/51 eyes while on medical treatment and 0/51 posttransplant (P<0.02). Conclusions. Progression of diabetic retinopathy was more likely to occur during medical therapy than after islet cell transplantation.

Controversies in Gestational Diabetes

Abstract Gestational diabetes (GD) occurs in women with a pre-existing abnormality of glucose metabolism. Although the O’Sullivan criteria were initially based on the development of Type II diabetes in the future, subsequent studies found adverse perinatal outcomes in women who had GD diagnosed by these criteria. Macrosomia in infants of mothers with GD is associated with more complications, both mechanical and metabolic, than in non-diabetics. A number of studies suggests that the O’Sullivan criteria are not strict enough and that typical diabetic complications can occur with lesser degrees of glucose intolerance. Study methods include showing a continuum of risk based on glucose tolerance test (GTT) values, retrospective evidence of increased glucose levels in mothers who delivered macrosomic infants, and abnormal outcomes in patients with untreated impaired glucose intolerance and patients with GTT normal by the O’Sullivan criteria but abnormal by the Coustan criteria. These studies indicate the need to screen universally for GD and to assess glucose metabolism in any patient showing evidence of macrosomia. With tight glucose control, normal outcomes can be achieved.

The Value of Treatment for Gestational Diabetes

Abstract: the concept of gestational diabetes mellitus (GDM) arose from the recognition of poor perinatal outcomes in women who went on to develop Type 2 diabetes. Early studies showed increased Perinatal mortality with untreated GDM and the reduction of mortality to normal with treatment. Many current studies continue to show increased perinatal morbidity with conventional treatment of GDM. Recent evidence suggests that poorly controlled GDM with macrosomic infants has long-term sequelae, including increased adolescent obesity and Type 2 diabetes. Tight glucose control has been shown to result in normal perinatal outcomes. Routine diagnosis and treatment of GDM have been shown to be an efficient use of health care resources, with three dollars saved for every dollar spent. We believe that a careful analysis of the literature clearly shows the benefit of routinely diagnosing and treating GDM. Resume : la notion de diabete sucre de la grossesse (DSG) est nee de la constatation du fait que les femmes atteintes du diabete de type II apres leur accouchement avaient eu de mauvais resultats perinatals. Les premieres etudes ont conclu que le DSG non traite produisait une augmentation du taux de mortalite perinatale et qu’il y avait une reduction de la mortalite lorsqu’il etait traite. Plusieurs etudes actuelles continuent de demontrer que le traitement du DSG par des methodes traditionnelles accroit la morbidite perinatale. Des resultats d’etudes recentes suggerent que le DSG mal maitrise chez les nouveau-nes de poids de naissance eleve entraine des sequelles a long terme, telles que l’obesite a l’adolescence et le diabete de type II. Il a ete demontre qu’un controle rigoureux du taux de glucose entraine des resultats perinatals normaux. On a aussi prouve que le diagnostic sytematique et le traitement du DSG constituent une utilisation des ressources des soins de sante de bon aloi puisqu’ils permettent d’epargner trois dollars pour chaque dollar depense. Nous croyons qu’une analyse approfondie de la litterature medicale demontre clairement les avantages du diagnostic systematique et du traitement du DSG.