insulin--isophane and Obesity

The goal of this post hoc analysis was to determine key patient and treatment-related factors impacting glycosylated hemoglobin (A1C) and hypoglycemia in patients with uncontrolled type 2 diabetes who were initiated to basal insulin (neutral protamine Hagedorn [NPH] or glargine).. Using individual patient-level data pooled from 6 treat-to-target trials, 2600 patients with type 2 diabetes on oral antidiabetic agents initiated to insulin glargine or NPH and treated for 24 to 36 weeks were analyzed.. Both treatments led to significant reduction in A1C levels compared with baseline, with no differences between treatment groups (mean ± standard deviation; glargine: -1.32 ± 1.2% vs NPH: -1.26 ± 1.2%; P = 0.15), with greater reduction in the BMI ≥30 kg/m group than in the BMI <30 kg/m group. Glargine reduced A1C significantly more than NPH in the BMI <30 kg/m group (-1.30 ± 1.18% vs -1.14 ± 1.22, respectively; P = 0.008), but not in the BMI ≥ 30 kg/m group (-1.37 ± 1.19 vs -1.48 ± 1.22, respectively; P = 0.18). Similar proportions of patients achieved A1C target of <7% (glargine 30.6%, NPH 29.1%; P = 0.39). Incidence of severe and severe nocturnal hypoglycemia was significantly lower in glargine versus NPH-treated patients (2.0% vs 3.9%; P = 0.04, and 0.7% vs 2.1%; P = 0.002, respectively), and occurred primarily in the BMI <30 kg/m group.. Initiation of basal insulin is highly effective in lowering A1C after oral antidiabetic agent failure. Glargine decreases A1C more than NPH in nonobese patients, and reduces the risk for severe and severe nocturnal hypoglycemia versus NPH both in obese and nonobese patients, but more so in nonobese patients. Thus, it is the nonobese patients who may benefit more from initiation of basal insulin as glargine than NPH.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Obesity; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

Primary care physicians are responsible for providing healthcare to most patients with type 2 diabetes. In this role, it is critical that physicians utilize a whole-patient treatment approach that includes lifestyle modifications and pharmacotherapy aimed to achieve glycemic control, in addition to the management of any comorbid conditions or risk factors for cardiovascular complications of diabetes. Due to the progressive nature of the disease, most patients with type 2 diabetes will eventually require insulin to achieve and maintain glycemic control, because of both increased insulin resistance and diminished secretory capacity of the pancreatic beta cells. Thus, physicians need to be knowledgeable about and comfortable with the use of insulin, as well as with educating patients and discussing any potential barriers to insulin therapy. The use of a stepwise approach--beginning with basal insulin therapy and adding prandial insulin if necessary--is simple, effective, and appropriate for use in many patients.

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Long-Acting; Life Style; Obesity; Physicians, Family; Risk Factors; Socioeconomic Factors; Treatment Outcome

The aim of study was to evaluate the safety and efficacy of insulin detemir as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and insulin glargine in patients with diabetes on an intensive insulin therapy regimen.. This 6-month multicentre, prospective, treat-to-target [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] trial included 92 people with diabetes (61 type 1, 29 type 2 and two unknown diabetes types). Detemir was administered first with fixed dose and injection times and then adapted to optimal dose after 3 months.. Mean HbA(1c) (%) of all the subjects at months 4 to 6 of the study was improved compared with month 0 (7.34 ± 0.87, 7.28 ± 0.88, 7.25 ± 0.93 vs. 7.55 ± 1.18; p < 0.05 paired t-test). However, significant improvement was seen only among the patients who had previously used NPH as a basal insulin. Twice-daily injection of basal insulin increased among people in the type 1 previously injected insulin glargine. Total insulin dose increased in the type 1 glargine group. The mean body weight change in the highest quartile body mass index (BMI) group was from 70.7 to 69.3 kg over the 6 months. Quality of life (QoL) relating to the patients' glycaemic control tended to improve without a change in frequency of hypoglycaemia.. The results suggest that insulin detemir has a greater effect on glycaemic control in subjects with poor glycaemic control using NPH; can reduce or maintain body weight in obese patients; and obtains perceptive stability for patients with unstable glycaemic control.

Topics: Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Obesity; Prospective Studies; Treatment Outcome; Weight Loss

Overweight and obesity are overrepresented in adolescents with type 1 diabetes mellitus (T1DM). Exogenous insulin administration often poorly reproduces normal insulin patterns and may less effectively regulate leptin and ghrelin, two hormones involved in the control of appetite and adiposity.. The objective of the study was to determine whether insulin regimens that better replicate normal insulin patterns and augment postprandial nutrient disposal may help normalize leptin and ghrelin and improve body weight regulation.. Ten young women with T1DM were studied in this 2-wk prospective, balanced crossover-design study at the University of California, Davis.. Participants received either a single injection of regular + NPH insulin (R+N) or two mealtime injections of Lispro insulin in randomized order on 2 separate days. Meal composition and total insulin administered were the same on both treatment days.. Plasma glucose, insulin, leptin, and ghrelin concentrations were monitored over the 10-h study period.. Lispro produced two distinct mealtime peaks of insulin, compared with one prolonged rise with R+N. Lispro reduced postprandial hyperglycemia and total glucose area under the curve. Leptin increased more on the Lispro (2.7 +/- 0.7 vs. 0.7 +/- 0.5 ng/ml, P = 0.02). Ghrelin was more suppressed after lunch with Lispro (P = 0.004).. Injection of Lispro insulin with meals produces more physiological insulin patterns, better glucose control, and improved leptin and ghrelin regulation than R+N. More closely mimicking normal insulin, leptin, and ghrelin responses to meals with fast-acting insulin may have implications for body weight regulation in T1DM.

Topics: Adolescent; Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Ghrelin; Humans; Insulin; Insulin Lispro; Insulin, Isophane; Leptin; Obesity; Peptide Hormones; Postprandial Period; Prospective Studies

To examine the safety and overall clinical effects of normalizing the fasting plasma glucose (FPG) level with bedtime NPH insulin alone in patients with non-insulin-dependent diabetes mellitus (NIDDM) that is poorly controlled with maximal doses of sulfonylureas.. Twelve obese male NIDDM subjects were treated for 16 weeks with bedtime insulin after a 4-week sulfonylurea washout. The insulin dosage was increased until the FPG level was normalized. The 24-h plasma glucose profiles and lipid and HbA1c levels were measured at the beginning and end of the study, and the incidence and severity of hypoglycemic episodes were closely monitored. In addition, hyperglycemic clamp studies were performed to assess insulin secretion and provide an indirect measurement of insulin sensitivity.. FPG (14.6 +/- 0.9 mmol/l at week 0) was normalized ( < 6.4 mmol/l) within 6 weeks (5.9 +/- 0.6 mmol/l) and remained at target levels until the end of the study (4.0 +/- 0.03 mmol/l at week 16, P < 0.001). The insulin dose was 80 +/- 9 U/day (0.86 +/- 0.10 U/kg). Improved glycemic control was confirmed by a reduction in HbA1c (10.9 +/- 0.05 vs. 7.2 +/- 0.2%, P < 0.001) and mean 24-h glucose (17.2 +/- 0.2 vs. 7.4 +/- 0.2 mmol/l, P < 0.001). The incidence of mild or moderate hypoglycemic episodes was 3.4 +/- 1/patient for the entire 16-week study, and no patient experienced severe hypoglycemia. Bedtime insulin significantly improved total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglyceride levels (P < 0.01). Weight gain was 2.4 +/- 0.7 kg, and blood pressure was unchanged. During the hyperglycemic clamp, there was an improvement in the first phase (P < 0.001) and in the second phase (P < 0.01) of insulin secretion. There also was an increase in the rate of exogenous glucose infused (M) (P < 0.01) and in the M/C-peptide ratio (P < 0.02), suggesting enhanced insulin sensitivity.. NPH insulin given at bedtime in amounts sufficient to achieve a normal FPG level does not cause excessive or severe hypoglycemia and does lead to good glycemic and lipid control in NIDDM. Bedtime insulin therapy also is accompanied by improved insulin secretion and insulin sensitivity. We conclude that a single dose of insulin alone at bedtime merits consideration as a therapeutic strategy in patients with poorly controlled NIDDM.

Topics: Analysis of Variance; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Glucose; Glycated Hemoglobin; Humans; Insulin, Isophane; Liver; Male; Middle Aged; Obesity; Reference Values; Time Factors; Triglycerides

To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas.. A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment.. Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients.. The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight.

Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Eating; Fasting; Glyburide; Glycated Hemoglobin; Humans; Insulin, Isophane; Metformin; Middle Aged; Obesity

Insulin requirements, C-peptide levels, and serum lipids have been assessed in 12 obese, insulin-requiring (greater than 60 U/day) patients with type II diabetes mellitus, in a randomized crossover fashion with two treatment regimens: NPH alone and combined NPH and tolazamide, over a period of 3 months each, with maintenance of weight and glycemic control (HgA1, 2hpp and mean 24h glucose profile) at comparable levels. Serum cholesterol improved in both groups compared to their respective baseline values (p less than 0.05). In addition, serum triglyceride was lower (p less than 0.05) in the combined therapy as compared with NPH alone therapy. Insulin requirements were decreased by 23% (p less than 0.002) in the combined therapy group, without significant change in weight, glycemic control, or C-peptide levels. However, C-peptide increments in the combined therapy group were significantly higher than the baseline by 70% (p less than 0.02). NPH plus tolazamide therapy as compared with NPH alone lowers insulin requirement in obese, type II diabetic women without significant alteration in glycemic control, possibly by an increased tissue sensitivity to insulin, and decreases serum triglyceride levels.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Insulin, Isophane; Middle Aged; Obesity; Prospective Studies; Random Allocation; Tolazamide; Triglycerides

Topics: Adult; Antipsychotic Agents; Comorbidity; Diabetes, Gestational; Dibenzothiazepines; Female; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Quetiapine Fumarate; Schizophrenia

Topics: Amino Acid Substitution; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Obesity

Combination therapy consisting of biphasic insulin aspart 30 bid with metformin provide better glycaemic control in obese patients with diabetes mellitus type 2. In our study, patients who were treated with 2550 mg of metformin, administered in three daily doses had poor glycaemic control. Three months after switching from metformin therapy to treatment with biphasic insulin aspart 30 + metformin twice a day, glycaemic control improved with significant reduction in hemoglobin HbA1c, fasting blood glucose and postprandial blood glucose levels. Biphasic insulin aspart 30 in combination with metformin administered twice a day may be recommended as a starting insulin treatment in obese diabetic persons whose glycaemic control remained poor while on oral metformin therapy alone.

Topics: Administration, Oral; Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Obesity; Treatment Outcome

In recent years, the approach to the insulin treatment of type 2 diabetics has undergone a change. Age and clinical status of the patient are decisive determinants for the selection of the appropriate form of treatment. The therapeutic strategy aims to achieve insulin substitution matched to the therapeutic objective, that is, continuous monitoring should be carried out to enable adaptation of the form and intensity of treatment to meet the target end point HbA1c < 6.5%. This necessity results in the earlier use of insulin in all, not only obese, type 2 diabetics. As a compromise solution, a certain percentage of these diabetics will have to be satisfied with simpler forms of insulin substitution and a higher HbA1c value. Attention is drawn to the other parameters of the metabolic syndrome, such as blood pressure, weight, and lipid metabolism. Particular importance attaches to non-pharmacological measures, in particular with the aim of avoiding a further increase in weight due to the treatment with insulin.

Topics: Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Obesity; Patient Education as Topic

To evaluate the possible benefits of the addition of intermediate-acting insulin administered at bedtime to therapy with daytime sulfonylureas in patients with non-insulin-dependent diabetes mellitus for whom maximal doses of oral hypoglycemic agents have not been successful.. Study subjects were 16 consecutive obese patients aged from 44 to 78 years (mean age, 62 years) with histories of non-insulin-dependent diabetes mellitus for a mean of 9 years. None of the subjects had been able to control their diabetes with maximal doses of oral hypoglycemic agents. All patients received 20 mg glipizide or 10 mg glyburide twice a day, as well as education about the American Diabetes Association diet. Neutral protamine Hagedorn (NPH) insulin was empirically added in doses from 0.1 to 0.2 units/kg given at bedtime. The dose was adjusted on the basis of fasting blood glucose levels.. Mean fasting blood glucose decreased from 13.7 +/- 3.4 to 8.3 +/- 2.7 mmol/L at 3 months and 7.3 + 2.0 mmol/L at 1 year. Glycosylated hemoglobin decreased from 9.0% +/- 1.9% to 6.2% +2- 1.16% at 3 months and 6.3% +/- 1.22% at 1 year.. A late-night dose of NPH insulin was added to a regimen of daytime sulfonylureas in a group of obese patients with type II diabetes whose hyperglycemia was not controlled with maximal doses of oral hypoglycemic agents. This treatment proved to be beneficial and is a useful alternative to conventional insulin therapy in this group of patients.

Topics: Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glipizide; Glyburide; Humans; Insulin, Isophane; Middle Aged; Obesity; Prospective Studies; Time Factors

The prolonged action of daily injections of beef ultralente insulin provides a source for the basal, steady state insulin supply which diabetics need in addition to their meal requirements. The complete distinction between basal and meal insulin requirements, provided by two or three injections of soluble insulin per day, allows simple rules to guide both the physician and patient. Thus, the required ultralente dose needs to be continued daily, irrespective of illness or missing meals, whereas the soluble insulin requirements are given according to meals. When starting ultralente insulin therapy a loading dose is required. The doses of ultralente and soluble insulin needed for different severities of diabetes and degrees of insulin resistance can be predicted. A simple regimen to cover the decreasing insulin requirements of newly presenting, ketotic juvenile-onset diabetics has been developed. During surgical operations the continued basal insulin supply, from ultralente insulin, greatly facilitates diabetes control. Whilst many patients have improved nocturnal blood glucose control after transfer to ultralente insulin, optimal control of diabetes sometimes remains difficult in view of the pre-breakfast plasma glucose rise and the longer action of subcutaneous soluble insulin than the physiological meal insulin response. Purified monocomponent beef ultralente insulin is antigenic, and human ultralente insulin might be advantageous.

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Pork; Obesity; Patient Education as Topic

Topics: Adult; Aged; Blood Glucose; Carbohydrate Metabolism; Chlorpropamide; Diabetes Mellitus; Drug Synergism; Female; Glycosuria; Humans; Insulin; Insulin Antibodies; Insulin Resistance; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Obesity; Phenformin; Tolbutamide

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Lente; Insulin, Long-Acting; Obesity; Statistics as Topic; Zinc