insulin--isophane and Diabetic-Nephropathies

Topics: Aged; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus; Diabetic Nephropathies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Predictive Value of Tests; Renal Dialysis; Time Factors

Monkeys with insulin-dependent diabetes are important preclinical animal models for islet transplantation. Exogenous insulin should be administered to achieve good glycemic control and minimize the long-term vascular complications associated with diabetes until the graft function recovered completely. However, the effect of multiple daily injections of porcine or human insulin and the long-term effects of porcine insulin have not been studied in diabetic rhesus monkeys.. Diabetic rhesus monkeys, using a 6-month self-control insulin comparison experiment, were used to detect the incidence of adverse events and long-term diabetes complication events after long-term administration of porcine insulin.. In this study, we found that a 20% higher dose of porcine insulin results in similar glycemic control as the human insulin regimen, and adverse events were seldom reported when porcine insulin was administered. Moreover, long-term injection with porcine insulin could delay the rate and severity of diabetes-related complications.. Porcine insulin as a competent candidate for regular insulin therapy to maintain blood glucose levels in insulin-dependent diabetic monkeys during preclinical studies of islet transplantation.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Glycated Hemoglobin; Hypoglycemic Agents; Insulin, Isophane; Insulin, Regular, Human; Insulin, Regular, Pork; Macaca mulatta; Monkey Diseases

In this rodent study, we compared the effects of early versus late intensive insulin therapy on diabetic nephropathy and potential causal mechanisms. Diabetes was induced in rats by high-fat diet and low-dose streptozotocin. Intensive insulin therapy was initiated in the early intensive insulin therapy groups as soon as diabetes was confirmed and lasted for 8 (8wEI group) and 16 weeks (16wEI group). In the late insulin therapy group (LI group), intensive insulin treatment was initiated 8 weeks later and lasted for 8 weeks. Age-matched diabetic rats (8wDM group and 16wDM group) and non-diabetic rats (8wNC group and 16wNC group) served as controls. Histological analysis, real-time PCR, and western blot were performed in renal cortex specimens. Glomerular hypertrophy and mesangial matrix expansion were prominent in the 16wDM and LI groups while the EI groups remained normal and similar to the 16wNC group. Western blots revealed that p38 MAPK activities in the EI groups decreased significantly, whereas the level in the LI group was markedly higher than the 16wEI group, and not different from the DM groups. Activities of MKK3/6, CREB and MKP-1 proteins as well as CREB and MKP-1 mRNA showed a similar pattern. Therefore, we concluded that early intensive insulin treatment and attainment of good glycemic control counteracted some renal molecular pathways associated with epigenetic metabolic memory to minimize risk of diabetic nephropathy. However, late insulin therapy did not abrogate the increased renal cortical p38 MAPK pathway activation in diabetic rats and led to glomerular hypertrophy and extracellular matrix expansion.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gene Expression Regulation; Glomerular Mesangium; Humans; Hypertrophy; Hypoglycemic Agents; Insulin, Isophane; Insulin, Regular, Human; Isophane Insulin, Human; Kidney Cortex; Kidney Glomerulus; Male; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Processing, Post-Translational; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors

It was decided to demonstrate by the present observations to which extent beneficial long-term effects on metabolic control, body weight and microalbuminuria can be attained by applying intensive insulin therapy (IIT) to type 2 diabetic patients, particularly when using insulin lispro.. In our observational study, clinical data were evaluated during 6, 12 and 36 months after participation in our structured inpatient insulin treatment and teaching programme in 25 patients with conventional insulin therapy (CT), in 10 patients with IIT using human normal insulin and in 15 patients with IIT using insulin lispro who all could be followed for 3 years in our outpatient diabetic clinic.. In the CT-treated patients, HbA1c decreased from 10.2 +/- 0.4% to 7.6 +/- 0.2% (average +/- SEM) after 3 years. Body weight increased from 27.8 +/- 0.9 kg/m2 to 28.6 +/- 0.9 kg/m2, insulin dose increased from 29 +/- 3 U/day to 48 +/- 5 U/day (all p < 0.05), urinary albumin concentration was only transiently reduced. In the IIT-treated patients using human normal insulin, HbA1c fell from 10.6 +/- 0.8% to 7.9 +/- 0.5%, body weight increased from 27.8 +/- 1.4 kg/m2 to 29.8 +/- 1.3 kg/m2, urinary albumin concentration was reduced from 26 +/- 10 mg/l to 13 +/- 3 mg/l (all p < 0.05). Insulin dose increased only slightly from 57 +/- 6 U/day to 63 +/- 7 U/day. In the IIT-treated patients using insulin lispro HbA1c fell from 8.4 +/- 0.5% to 6.7 +/- 0.3%, body weight increased from 27.6 +/- 1.0 kg/m2 to 28.7 +/- 1.3 kg/m2, insulin dose from 36 +/- 5 U/day to 50 +/- 7 U/day, urinary albumin concentration was reduced from 23 +/- 4 mg/l to 13 +/- 4 mg/l (all p < 0.05). Blood pressure remained uninfluenced by insulin therapy.. In our patients, we observed a beneficial long-term effect on metabolic control of IIT-treatment using insulin lispro, which was evident over the complete 3-year observation period, together with an only moderate increase in insulin dose and a clinically acceptable increase in body weight, but a remarkable reduction of microalbuminuria. Thus, clinical outcome was superior to that in patients treated with CT or IIT using human normal insulin.

Topics: Aged; Albuminuria; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Kidney Function Tests; Male; Metformin; Middle Aged; Treatment Outcome

Topics: Abscess; Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Insulin, Isophane; Proteus Infections; Pyelonephritis; Rats