Intensive Metabolic Control Research Articles

Effect of 48 Months of Closed-Loop Insulin Delivery on Residual C-Peptide Secretion and Glycemic Control in Newly Diagnosed Youth With Type 1 Diabetes: A Randomized Trial.

We evaluated the effect of long-term intensive metabolic control with hybrid closed-loop (CL) on residual C-peptide secretion and glucose control compared with standard insulin therapy in youth with type 1 diabetes over 48 months. Following the 24-month primary phase of a multicenter, randomized, parallel trial of 96 newly diagnosed youth aged 10 to 16.9 years, participants were invited to an extension phase using treatment allocated at randomization. They continued with hybrid CL using the Cambridge algorithm or standard insulin therapy (control) until 48 months after diagnosis. Analysis was by intention-to-treat. At 24 months after diagnosis, 81 participants (mean ± SD age 14 ± 2 years) continued in the extension phase (47 CL, 34 control). There was no difference in fasting C-peptide corrected for fasting glucose at 48 months between groups (CL: 5 ± 9 vs. control: 6 ± 14 pmol/L per mmol/L; mean adjusted difference -2 [95% CI -7, 4; P = 0.54]). Central laboratory HbA1c remained lower in the CL group by 0.9% (10 mmol/mol [95% CI 0.2, 1.5; 3, 17 mmol/mol); P = 0.009). Time in target range of 3.9 to 10.0 mmol/L was 12 percentage points (95% CI 3, 20; P = 0.008) higher in the CL group compared with control. There were 11 severe hypoglycemic events (6 CL, 5 control) and 7 diabetic ketoacidosis events (3 CL, 4 control) during the extension phase. Improved glycemic control was sustained over 48 months after diagnosis with CL insulin delivery compared with standard therapy in youth with type 1 diabetes. This did not appear to confer a protective effect on residual C-peptide secretion.

Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol

IntroductionManagement of newly diagnosed type 1 diabetes (T1D) in children and adolescents is challenging for patients, families and healthcare professionals. The objective of this study is to determine whether continued...

Assessment of a Multidisciplinary Intervention in Patients With BMI ≥35 kg/m2 and Recently Diagnosed Type 2 Diabetes.

Patients with a body mass index (BMI) ≥35 kg/m2 have lower benefits with intensive treatments and metabolic control goals are more difficult to reach. Evaluate the effect of a comprehensive care program in patients with a BMI ≥35 kg/m2. Prospective cohort study. Comprehensive Care Center in a National Institute of Health. Patients with type 2 diabetes, ≤5 years of diagnosis, without disabling complications, nonsmokers, and a BMI <45 kg/m2. Exercise and nutritional interventions are modified for patients with a higher BMI to achieve metabolic control. Main outcome is achievement of treatment goals defined as HbA1c <7%, low-density lipoprotein cholesterol (LDL-c) <100 mg/dL, and blood pressure <130/80 mm Hg. Secondary measures were the percentage of patients achieving three metabolic goals. A total of 587 patients with annual evaluation were included. Mean age was 55.3 ± 9.5 years, 56.6% women, time since diagnosis of 1 year (0 to 5). BMI <35 kg/m2 group included 521 patients and BMI ≥35 kg/m2 group included 66 patients. In the BMI ≥35 kg/m2 group, we observed a greater decrease in weight and fat mass at 3 months compared with <35 kg/m2 group, but the HbA1c, LDL-c, or blood pressure goals were similar at 3 months and 1 year between groups. Comprehensive interventions are equally effective in patients with recently diagnosed type 2 diabetes with BMI ≥35 kg/m2 compared with patients with a lower BMI.

Intensive Metabolic Control of T1D Pregnant Women in CSII vs. MDI—A Retrospective Analysis

Diabetes-complicated pregnancy requires intensive gluco-metabolic monitoring. There is no clear evidence that insulin pump therapy (CSII) is superior to multiple daily injections with insulin analogs (MDI) in achieving tight glycemic control. We conducted a retrospective analysis on 72 (69 singles and 3 twins) T1D pregnant women, followed at the Diabetes and Pregnancy Unit (University Hospital, Perugia) since the first weeks of gestation or before conception. Maternal metabolic parameters (HbA1c, mean BG, weight gain, prandial and basal insulin needs and percentage increase in insulin requirement, I:CHO ratio) at conception, and each trimester, were assessed. Finally, neonatal outcomes (birth weight, newborn age, neonatal complications-malformations incidence) were analyzed. We compared the data with regard to applied regimens (CSII vs. MDI). 28 women were on CSII (38.8%) and 44 on MDI therapy, with mean HbA1c at conception of 7.1 ± 0.7% vs. 7.2 ± 1.2%, respecively (P&amp;gt; 0.05). Women who received pre-conceptional counseling (56% of CSII women vs. 13% of MDI), showed significantly lower HbA1c at conception (6.7 ± 0.6 vs. 7.3 ± 1.1, p &amp;lt;0.05). Disease duration, previous abortion rate and prevalence of chronic complications (class D-G, White classification) were significantly higher in CSII group. In single pregnancies, no significant differences were observed, in CSII vs. MDI, as far as HbA1c, insulin (U/Kg), percentage increase of insulin requirement, I:CHO ratio, weight increase, gestation term, birth weight, prevalence of maternal and neonatal complications were concerned (p&amp;gt; 0.05). CSII was not proved superior to MDI in the management of pregnancy, in terms of neither maternal insulin requirements nor of maternal-fetal outcomes. Intensive management of diabetic pregnancy ensures stringent glycemic control, regardless of treatment with CSII or MDI. The choice of treatment modality should be targeted on pre-gestational and individual parameters. Disclosure S. Parrettini: None. I. Giardina: None. F. Cardini: None. E. Torlone: Other Relationship; Self; Medtronic MiniMed, Inc., Novo Nordisk Inc., Eli Lilly and Company, Roche Diabetes Care Health and Digital Solutions, Sanofi-Aventis, Menarini Group.

Effect of an intensive metabolic control lifestyle intervention in type-2 diabetes patients

ObjectiveTo evaluate the effectiveness of an intensive lifestyle intervention on metabolic control in patients with type 2 diabetes. Methods199 patients recently diagnosed with type 2 diabetes, with lack of metabolic control and overweight/obesity, were randomly assigned to intensive lifestyle intervention or collaborative educational program alone, with 6 months of follow-up. Intervention included 150min of physical activity a week to reduce body weight by 7%. Both groups received 16 sessions on behavior modification over the course of the 6 months. Measurements were taken at baseline, 3 and 6 months. Results were analyzed and compared. ResultsSignificant weight loss was achieved by both groups, with greater loss in the intervention group. Those with lower baseline A1c appeared to benefit more from the educational program than intensive intervention over time. ConclusionsBoth interventions produced positive if modest changes in metabolic control. These results suggest that, for weight loss and control of A1c, an intensive intervention may be more effective. Practice ImplicationsThe current study demonstrates the value of a systematic application of behavior modification and self-care techniques in the treatment of type 2 diabetes. It demonstrates the importance of intensive, all-inclusive treatment, and of attention to individual concerns.

Diabetic Retinopathy and Diabetic Macular Edema.

Diabetic retinopathy and diabetic macular edema result from chronic damage to the neurovascular structures of the retina. The pathophysiology of retinal damage remains uncertain but includes metabolic and neuroinflammatory insults. These mechanisms are addressed by intensive metabolic control of the systemic disease and by the use of ocular anti-inflammatory agents, including vascular endothelial growth factor inhibitors and corticosteroids. Improved understanding of the ocular and systemic mechanisms that underlie diabetic retinopathy will lead to improved means to diagnose and treat retinopathy and better maintain vision.

Effect of intensive glycemic control on platelet reactivity in patients with long-standing uncontrolled diabetes

BackgroundIt has been previously shown that platelets of patients with diabetes are more reactive and less responsive to anti-platelet drugs compared with platelets from subjects without diabetes. Studies examining the effect of glycemic control on platelet reactivity have yielded conflicting data. Thus, in this study, we sought to explore the effect of tight glycemic control on platelet reactivity in patients with long standing uncontrolled diabetes. MethodsThe study included 30 patients with long-standing treated diabetes and a baseline HbA1c level of≥8.5%. All patients were treated with aspirin and statins. Patients were tested at baseline and after 3months of intensive glycemic and metabolic control. The treatment goal was to achieve a HbA1c level of ≤7%. Platelet reactivity was assessed by light transmission aggregation in response to 5 and 10μM ADP and to 0.5mg/ml arachidonic acid (AA). Additonally, platelet activation was assessed by plasma levels of soluble P-selectin using an enzyme-linked immunosorbent assay. ResultsThe mean duration of diabetes from the time of diagnosis was 20.46±9.31years. Baseline HbA1c was 9.4±0.8%. Following the intensive glycemic control period, the HbA1C level decreased to 8.1±0.8% (P<0.0001). Other laboratory parameters did not change significantly except for triglyceride levels, which decreased. None of the platelet aggregation studies nor P-selectin levels differed between baseline and after 3months of intensive glycemic control. ConclusionsIntensive glycemic control in patients with longstanding uncontrolled diabetes does not seem to result in a reduction in platelet reactivity.

Pathophysiology and treatment of diabetic retinopathy

In the past years, the management of diabetic retinopathy (DR) relied primarily on a good systemic control of diabetes mellitus, and as soon as the severity of the vascular lesions required further treatment, laser photocoagulation or vitreoretinal surgery was done to the patient. Currently, even if the intensive metabolic control is still mandatory, a variety of different clinical strategies could be offered to the patient. The recent advances in understanding the complex pathophysiology of DR allowed the physician to identify many cell types involved in the pathogenesis of DR and thus to develop new treatment approaches. Vasoactive and proinflammatory molecules, such as vascular endothelial growth factor (VEGF), play a key role in this multifactorial disease. Current properly designed trials, evaluating agents targeting VEGF or other mediators, showed benefits in the management of DR, especially when metabolic control is lacking. Other agents, directing to the processes of vasopermeability and angiogenesis, are under investigations, giving more hope in the future management of this still sight-threatening disease.

Obstetric Nephrology

This review highlights factors of importance for the clinical care of pregnant women with pregestational diabetes and microalbuminuria or diabetic nephropathy with particular focus on the role of intensive antihypertensive treatment during pregnancy. Most information in the literature comes from women with type 1 diabetes and diabetic nephropathy, but this is probably also valid for women with type 2 diabetes. Careful counseling of women with diabetic nephropathy before pregnancy with estimation of the risk for the mother and fetus is important. Pregnancy does not result in worsening of kidney function in women with diabetic nephropathy and normal serum creatinine, but pregnancy complications such as pre-eclampsia and preterm delivery are common. Intensive metabolic control before and during pregnancy, low-dose aspirin from 12 gestational weeks onward, and intensive antihypertensive treatment are important. Methyldopa, labetalol, and nifedipine are regarded safe in pregnancy, whereas angiotensin converting enzyme inhibitors, AngII antagonists, or statins should be paused before pregnancy. Case series and pathophysiological studies support the use of a stringent goal for BP and albumin excretion in pregnant women with diabetic nephropathy. Screening for diabetic retinopathy before and during pregnancy is mandatory and laser treatment should be performed if indicated. Pregnancy outcome in women with diabetic nephropathy has improved considerably with a take-home-baby rate of approximately 95%. Further research on the benefits and risks of intensive antihypertensive treatment in this population is needed.

Nrf2 Activators as Attractive Therapeutics for Diabetic Nephropathy

Diabetes is the major cause of chronic kidney disease worldwide (1) with treatment options focused primarily on glucose control, blood pressure, lipid lowering, and the blockade of the renin-angiotensin system (2). However, despite intensive metabolic control and other interventions (3), the unrelenting decline in kidney function means that for many patients the condition progresses to overt kidney failure. This underpins the urgent need for novel approaches to manage the ever-increasing number of patients with diabetes and chronic kidney disease. One approach that is attracting attention is the use of compounds to bolster the natural cytoprotective responses of the body. The transcription factor NF-E2–related factor 2 (Nrf2), together with its negative regulator, Kelch-like ECH-associated protein 1 (Keap1), is considered one of the most important cellular defense mechanisms to combat oxidative stress (4) with a particular role in the regulation of phase II detoxifying enzymes (Fig. 1). In particular, NADPH quinone oxidoreductase, glutathione S -transferase, heme oxygenase-1, and γ-glutamylcysteine synthetase are well-studied targets of Nrf2 that are upregulated through the antioxidant response element found in the promoters of these genes (5). Therefore, the coordinated upregulation of genes coding for detoxification, antioxidant, and anti-inflammatory regulators is seen as a potential therapeutic strategy to protect against insults such as inflammation and oxidative stress that are …

Características clínicas e laboratoriais associadas à nefroangioesclerose hipertensiva confi rmada por biópsia renal

Hypertensive nephroangiosclerosis is a major cause of chronic kidney disease requiring dialysis. Clinical characteristics that distinguish a patient with hypertension that evolves to nephroangiosclerosis from another that keeps stable renal function are not well established because of the difficulty in ensuring that the carriers of that disease are not actually suffering from glomerulonephritis or other kidney diseases. Thus, our objective was to identify clinical or laboratory features that distinguish the patients who developed chronic renal failure from hypertension, confirmed by renal biopsy, of those who, even with arterial hypertension, did not develop nephroangiosclerosis. We conducted a retrospective comparison of clinical and laboratory data of 15 patients with hypertensive nephroangiosclerosis confirmed by renal biopsy and 15 hypertensive patients from the outpatient clinic of the Hypertension Center, whose lack of nephroangiosclerosis was defined as absence of proteinuria. The groups were matched for age and gender. Among the evaluated variables, duration of hypertension, pulse pressure, blood glucose, uric acid, creatinine and frequency of use of diuretics and sympatholytic differed statistically between the two groups. All these variables were higher in nephroangiosclerosis patients. This study links biopsy proven hypertensive nephroangiosclerosis with metabolic features, hypertension intensity and duration, corroborating the idea that primary prevention of hypertension, postponing its initiation, a more intensive hemodynamic control (when hypertension is well established) and metabolic control of these patients have the potential to prevent hypertensive nephroangiosclerosis.

Short report: suboptimal diabetes care in high‐risk diabetic patients attending a specialist retina clinic

Individuals with diabetic retinopathy (DR) represent a high-risk group who would benefit from intensive metabolic control and risk factor management. This brief report examines quality of care among diabetic patients attending a tertiary retinal clinic. A cross-sectional survey, notes review, and slit-lamp examination was conducted in 139 diabetic patients attending a specialist retinal clinic to assess the quality of comprehensive diabetes care. DR was graded according to the Early Treatment Diabetic Retinopathy Study scale. The prevalence of non-proliferative DR (NPDR) and proliferative DR (PDR) was 39.6 and 35.2%, respectively. The prevalence of microalbuminuria in patients with no DR, NPDR and PDR was 32, 54.1 and 68.8%, respectively. Glycaemic control was suboptimal (mean HbA(1c) 8.0 +/- 1.8%) and 15.8% were current smokers. Drugs affecting the renin-angiotensin system were used by only 61.9% of patients with both DR and microalbuminuria, and aspirin by only 35.3%. These data suggest that diabetes care in this high-risk population with established microvascular complications was suboptimal. Specialist clinics dealing with diabetic complications may be a setting where quality improvement strategies to reduce morbidity and mortality should be focused.

Renal p38 MAP kinase activity in experimental diabetes

Renal cell activity of p38 mitogen-activated protein kinase (p38) is increased in the diabetic milieu. p38 mediates signals relevant for the development of diabetic nephropathy (DN). However, renal p38 in Type 1 diabetes in vivo, particularly in conditions reflecting the differences in metabolic control, and its activity in advanced stages of DN, has received less attention. We examined the p38 pathway in renal cortex of rats with streptozotocin diabetes (4 weeks) with poor (DS), moderate (DM), and intensive (DII) metabolic control, achieved by varying doses of insulin therapy. Renal p38 was also studied in 12-month diabetic rats with established nephropathy (DM12) and compared with age-matched controls. p38 activity (in vitro kinase assay and expression of phosphorylated (active) p38 (P-p38)) was increased in DM and DS rats, as compared with non-diabetic controls, and attenuated by intensive insulin treatment. In all groups, P-p38 was predominantly localized in macula densa cells. Diabetic rats also demonstrated P-p38 immunoreactivity in the distal tubule and glomeruli. Enhanced p38 activity in DS and DM rats was not associated with increases in expression of active mitogen-activated protein kinase 3/6, an activator of p38, but paralleled with increased expression of scaffolding protein transforming growth factor-β-activated protein kinase 1-binding protein 1. Expression of mitogen-activated protein phosphatase-1 (MKP-1), one of the phosphatases involved in inactivation of mitogen-activated protein kinase signaling, was increased in all diabetic groups, irrespective of metabolic control. Renal p38 activation was also detectable in D12 rats with established albuminuria and glomerulosclerosis. In summary, renal cortical p38 activity was increased in diabetic rats at early and advanced stages of nephropathy, as compared with non-diabetic animals, and attenuated by improved metabolic control. p38 activation in diabetes is likely to occur via multiple pathways and cannot be explained by downregulation of MKP-1.

Role of Insulin-Glucose Infusion in Outcomes After Acute Myocardial Infarction: The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) Study

ObjectiveTo review the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study for findings regarding effects on morbidity and mortality. ResultsThe DIGAMI trial was an intervention study that tested the hypothesis that initial intensive metabolic control by insulin-glucose infusion for at least 24 hours followed by long-term treatment with subcutaneously administered insulin improved the prognosis in patients with diabetes and acute myocardial infarction. Overall, the intensive approach reduced the long-term relative mortality (at 3.4 years of follow-up) by 25% in the insulin-treated group. Improved long-term survival was especially evident in the prestratified group of patients without prior insulin treatment, in whom the 3.4-year mortality reduction was 45%. Furthermore, a close correlation was noted between high blood glucose level at admission and mortality among the patients in the control group; this relationship was attenuated by intensive insulin treatment. ConclusionThe DIGAMI study supports the theory that intensive metabolic care in patients with diabetes who have had an acute myocardial infarction improves the prognosis. The study, however, could not answer whether this result was due to the initial insulin-glucose infusion or to the long-term subcutaneous treatment with insulin. This question is currently being addressed in the DIGAMI-2 study. (Endocr Pract. 2004;10[Suppl 2]:13-16)

Hypoglycemia associated autonomic failure.

Intensively treated patients with diabetes have a three-fold increased risk of severe hypoglycemic episodes with an attendant four percent mortality. These findings, unfortunately undermine attempts to achieve normoglycemia in diabetic patients. It has been proven that antecedent hypoglycemia is a major factor responsible for blunting metabolic, neuroendocrine and also autonomic responses to subsequent hypoglycemia. Diabetic patients with good glycemic control become unable to recognize symptoms of hypoglycemia. Lack of symptoms, or hypoglycemia unawareness, is part of the syndrome called hypoglycemia associated autonomic failure. This syndrome also includes inadequate neuroendocrine hormonal responses and reduced glycemic thresholds for counterregulatory hormonal secretion. Factors regulating the magnitude of hypoglycemia associated autonomic failure include antecedent duration and frequency of hypoglycemia, prior episodes of exercise, and autonomic neuropathy. Understanding the pathophysiology of this syndrome will provide a foundation for therapy aimed at preventing severe hypoglycemia during intensive metabolic control. This article will review our current understanding of the mechanisms responsible for hypoglycemia associated autonomic failure.

Glucose counterregulation in Type 2 diabetes mellitus.

Glucose counterregulatory failure and hypoglycaemia unawareness frequently complicate treatment of Type 1 diabetes mellitus, especially when aiming for intensive metabolic control. Since tight metabolic control reduces microvascular long-term complications in Type 2 diabetes mellitus, the integrity of glucose counterregulation in Type 2 diabetic patients is important. Using a Medline search, we identified 12 studies in which counterregulatory responses to insulin-induced hypoglycaemia were compared between Type 2 diabetic patients and appropriate controls. A review of these studies showed that some patients with Type 2 diabetes mellitus develop mild counterregulatory dysfunction and reduced awareness of insulin-induced hypoglycaemia. Some studies suggested an association between counterregulatory impairment and intensity of metabolic control. We speculate that the relatively low frequency of (severe) hypoglycaemic events in Type 2 diabetes may explain why glucose counterregulation remains unaffected in most patients. We hypothesize that residual beta-cell reserve and insulin resistance provide protection against severe hypoglycaemia and limit impaired counterregulation. Diabet. Med. 18, 519-527 (2001)

The relationship between physicians' self-reported target fasting blood glucose levels and metabolic control in type 2 diabetes. The QuED Study Group--quality of care and outcomes in type 2 diabetes.

To investigate the relationship between beliefs of physicians relative to intensive metabolic control in type 2 diabetes and levels of HbA1c obtained in a sample of their patients. Physicians' beliefs were investigated through a questionnaire sent to a sample of self-selected clinicians participating in a nationwide initiative aimed at assessing the relationship between the quality of care delivered to patients with type 2 diabetes and their outcomes. At the same time, physicians were asked to collect clinical data on a random sample of their patients, stratified by age (<65 vs. > or = 65 years). Mean HbA1c levels in the study population were thus evaluated according to target fasting blood glucose (FBG) used by their physicians. Of 456 physicians, 342 (75%) returned the questionnaire. Among the responders, 200 diabetologists and 99 general practitioners (GPs) recruited 3,297 patients; 2,003 of whom were always followed by the same physician and 1,294 of whom were seen by different physicians in the same structure on different occasions. Only 14% of the respondents used target FBG levels < or = 6.1 mmol/l, whereas 38% pursued values >7.8 mmol/l, with no statistically significant difference between diabetologists and GPs. The analysis of the relationship between FBG targets and metabolic control, restricted to those patients always seen by the same physician, showed a strong linear association, with mean HbA1c values of 7.0 +/- 1.6 for patients in the charge of physicians pursuing FBG levels < or = 6.1 mmol/l and 7.8 +/- 1.8 for those followed by physicians who used target values >7.8 mmol/l. After adjusting for patients' and physicians' characteristics, the risk of having HbA1c values > 7.0% was highly correlated with physicians' beliefs. Patients followed by different physicians in the same unit showed a risk of inadequate metabolic control similar to that of patients followed by physicians adopting a nonaggressive policy. Doctors adopt extremely heterogeneous target FBG levels in patients with type 2 diabetes, which in turn represent an important independent predictor of metabolic control. To improve patient outcomes, physicians-centered educational activities aimed at increasing the awareness of the potential benefits of a tight metabolic control in patients with type 2 diabetes are urgently needed.

Continuous subcutaneous insulin therapy during early pregnancy

Intensive metabolic control of diabetes is probably important during formation of the embryo early in pregnancy. The purpose of this study was to determine the efficacy and complications of continuous subcutaneous insulin infusion therapy during the fifth to the tenth week of gestation. Twenty-four insulin-dependent subjects were trained to use blood glucose self-monitoring and the Auto Syringe portable insulin infusion pump (AS6C). Regular insulin was administered as a basal infusion of 18 +/- 8 U/24 hours (+/- SD) (12.2 +/- 3.9 mU . kg-1 . h-1) and as bolus injections of 6 +/- 3 U before meals and 1.2 +/- 1 U before snacks. Reasonable control of fasting (119 +/- 30 mg/dL) and postprandial (133 +/- 34 mg/dL) hyperglycemia was achieved, accompanied by an average of 2.2 +/- 1.5 symptomatic hypoglycemic episodes per week. The frequency of complications with this new therapy declined as the authors gained experience in teaching the system. The persistence of good diabetic control in many of the subjects after they returned to conventional insulin therapy points to the need for a controlled trial of continuous subcutaneous insulin infusion therapy versus intensive conventional therapy in pregnancy.

End-state renal failure in diabetic nephropathy: pathophysiology and treatment.

Forty percent of patients with insulin-dependent diabetes will develop nephropathy during the course of their disease, thus being the most important single disorder leading to end-stage renal failure (ESRF). Intensive metabolic control delays onset of diabetic nephropathy, the first omen of which is appearance of subclinical albuminuria, also termed microalbuminuria. Moreover, it is now established that intensive treatment of hypertension reduces rate of decline in GFR and thus postpones ESRF. When uremia eventually sets in, a range of biochemical and endocrine abnormalities can be included among those characteristics of diabetes mellitus per se. These include elevated plasma levels of growth hormone, glucagon and free fatty acids, which may participate in the uremic insulin resistance superimposed on the preexisting diabetic carbohydrate intolerance. Hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) are two established modalities of renal replacement therapy in diabetes mellitus. Controlled clinical trials for comparison of CAPD versus HD treatment of diabetics are, however, still needed. The survival rate is approximately 80 and 65-95% in insulin-dependent diabetic patients at 1 year during treatment with HD and CAPD, respectively. However, it is general experience that diabetics on CAPD exhibit a glycemic control, superior to that attained during HD. It has not been proved that patient survival after cadaveric renal transplantation is better than on dialysis. The degree of vascular heart disease seems to be the major determinant for survival of kidney-transplanted diabetic patients.

Investigation on serum C-peptide concentrations in pregnant diabetic women and in newborns of diabetic mothers.

Serum C-peptide concentrations at delivery and neonatal complications were investigated in a group of diabetic mothers and in their infants (IDM, n = 29). Furthermore, the changes in B-cell function and in daily insulin demand was followed up in 12 pregnant diabetics (of them 8 with long-term and 4 with short-term and "mild" diabetes) during pregnancy. All these diabetic mothers were under an intensive metabolic control with the aim to achieve normoglycaemia mainly in the second part of pregnancy. Mean cord blood C-peptide level of 29 IDM was 0,58 +/- 0,43 nmol/l, being not significantly higher than either the average C-peptide concentration of our adult control group (0,50 +/- 0,15 nmol/l, n = 24) or that of seven infants born to healthy mothers (0,58 +/- 0,37 nmol/l). Early hypoglycaemia was observed in five, macrosomia in three and IRDS in one neonate, resp. mothers coming to our intensive care after the 13th week of gestation gave birth with a higher incidence of neonatal complications than those controlled already in the first trimester or even preconceptionally. In 20 of 25 mothers studied venous C-peptide concentrations at delivery were undetectably low, in spite of their infants having cord blood C-peptide levels in the measurable range. In 8 of the 12 diabetic mothers with long-term diabetes C-peptide levels remained under the detection limit of the assay throughout pregnancy. In the 4 other cases with "mild" diabetes (and, hence, with a late start of intensive control) C-peptide values increased in the course of pregnancy; however, 3 of the four mothers gave birth with neonatal complications. These results indicate that (1) early--preferably preconceptional--intensive metabolic control of pregnant diabetics may reduce the incidence of neonatal complications; (2) fetal C-peptide can neither during pregnancy nor at birth pass through the placental barrier, and (3) mothers with "mild" diabetes require the same early and strict metabolic control as the more severe cases to avoid neonatal complications.