symptoms of child diabetes

This study began in 1977 as a multicenter clinical trial designed to establish, in type 2 diabetic patients, whether the risk of macrovascular or microvascular complications could be reduced by intensive blood glucose control with oral hypoglycemic agents or insulin and whether any particular therapy was of advantage. Newly diagnosed type 2 diabetic patients aged 25-65 years were recruited between 1977 and 1991, and a total of 3867 were studied over 10 years. The median age at baseline was 54 years; 44% were overweight (> 120% over ideal weight); and baseline HbA1c was 9.1%. Therapies were randomized to include a control group on diet alone and separate groups intensively treated with either insulin, chlorpropamide, glyburide, or glipizide. Metformin was included as a randomization option in a subgroup of 342 overweight patients, and much later in the study an additional subgroup of both normal-weight and overweight patients who were responding unsatisfactorily to sulfonylurea therapy were randomized to either continue on their sulfonylurea therapy alone or to have metformin combined with it.
In 1987, an additional modification was made to evaluate whether tight control of blood pressure with stepwise antihypertensive therapy would prevent macrovascular and microvascular complications in 758 hypertensive patients among this UKPDS population compared with 390 of them whose blood pressure was treated less intensively. The tight control group was randomly assigned to treatment with either an angiotensin-converting enzyme (ACE) inhibitor (captopril) or a ß-blocker (atenolol). Both drugs were stepped up to maximum dosages of 100 mg/d and then, if blood pressure remained higher than the target level of < 150/85 mm Hg, more drugs were added in the following stepwise sequence: a diuretic, slow-release nifedipine, methyldopa, and prazosin — until the target level of tight control was achieved. In the control group, hypertension was conventionally treated to achieve target levels < 180/105 mm Hg, but these patients were not prescribed either ACE inhibitors or ß-blockers.
Intensive glycemic therapy in the entire group of 3897 newly diagnosed type 2 diabetic patients followed over 10 years showed the following: Intensive treatment with either sulfonylureas, metformin, combinations of those two, or insulin achieved mean HbA1c levels of 7%. This level of glycemic control decreases the risk of microvascular complications (retinopathy and nephropathy) in comparison with conventional therapy (mostly diet alone), which achieved mean levels of HbA1c of 7.9%. Weight gain occurred in intensively treated patients except when metformin was used as monotherapy. No cardiovascular benefit and no adverse cardiovascular outcomes were noted regardless of the therapeutic agent. Hypoglycemic reactions occurred in the intensive treatment groups, but only one death from hypoglycemia was documented during 27,000 patient-years of intensive therapy.
When therapeutic subgroups were analyzed, some unexpected and paradoxical results were noted. Among the obese patients, intensive treatment with insulin or sulfonylureas did not reduce microvascular complications compared with diet therapy alone. This was in contrast to the significant benefit of intensive therapy with these drugs in the total group. Furthermore, intensive therapy with metformin was more beneficial in obese persons than diet alone with regard to fewer myocardial infarctions, strokes, and diabetes-related deaths, but there was no significant reduction by metformin of diabetic microvascular complications as compared with the diet group. Moreover, in the subgroup of obese and nonobese patients in whom metformin was added to sulfonylurea failures, rather than showing a benefit, there was a 96% increase in diabetes-related deaths compared with the matched cohort of patients with unsatisfactory glycemic control on sulfonylureas who remained on their sulfonylurea therapy. Chlorpropamide also came out poorly on subgroup analysis in that those receiving it as intensive therapy did less well as regards progression to retinopathy than those conventionally treated with diet.
Intensive antihypertensive therapy to a mean of 144/82 mm Hg had beneficial effects on microvascular disease as well as on all diabetes-related end points, including virtually all cardiovascular outcomes, in comparison with looser control at a mean of 154/87 mm Hg. In fact, the advantage of reducing hypertension by this amount was substantially more impressive than the benefit achieved by improving the degree of glycemic control from a mean HbA1c of 7.9% to 7%. More than half of the patients needed two or more drugs for adequate therapy of their hypertension, and there was no demonstrable advantage of ACE inhibitor therapy over therapy with ß-blockers with regard to diabetes end points. Use of a calcium channel blocker added to both treatment groups appeared to be safe over the long term in this diabetic population despite some controversy in the recent literature about its safety in diabetics. (current MD&T 2005)