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The glycemic index: variation between subjects and predictive difference.

It is not known whether the variability of the glycemic index (GI) in different subjects is due to within- or between-individual variation. In addition, it is not known how large a difference in GI between different meals is clinically important for individuals with diabetes. Therefore, insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic subjects tested four foods, with each food taken by each subject on two separate occasions. For each food, most of the variation of absolute glycemic responses was due to differences between the subjects. However, when the results were expressed as the GI, there were no significant differences between the subjects, and most of the variation was due to within-individual variation. Using the within-individual variance, we estimated the so-called "predictive difference" of GI values. Its reliability was assessed by consideration of published data from eight studies where different mixed meals were taken by the same group of subjects. There were 37 cases where the difference between the GI of any two meals was greater than the predictive difference. Of these 37 pairs of meals, the GI correctly ranked the glycemic responses in 36 (97%). We conclude that GI values for the same food do not vary significantly between different individuals. For a subject with NIDDM a difference in GI of 34 will predict the ranking of glycemic responses of two meals with 95% probability. The corresponding value for a subject with IDDM is 50.

Blood Glucose↗

[How to measure glycemic instability?].

Instability of glycemic levels is "normal" in type 1 diabetes, with different levels of severity, up to the restrictive definition of brittle diabetes (repeated ketoacidosis and/or severe hypoglycemias). Quantification of glycemic instability, in terms of intraday variability and day-to-day reproducibility, is advisable. Standard deviation of blood glucose, though a simple index does not discriminate between slow and brutal variations. Repartition of blood glucose values also only indicates dispersion. M values compares the patient values to an ideal blood glucose level, emphasizing the role of low values. The MAGE index measures the amplitude of the largest glucose excursions, thus evaluating appropriately glycemic variability. The Low Blood Glucose Index (LBGI) is a new index of variability emphasising (as the M value) the low glycemias. Each glycemia is given a value from O (if >=110 mg/dl) to 100 (if 20 mg/dl). It thus integrates the frequency and severity of hypoglycemias. According to its authors the LBGI would be the best indicator of severe hypoglycemias. The Mean of Daily Differences (MODD) evaluates the day-to-day reproducibility of blood glucose values. All the above indexes could easily be incorporated in the programmes of large memory glucose meters.

Blood Glucose↗

The effects of low-dose Bay-m-1099 (Miglitol) on serum lipids and liver enzyme activity of obese and obese-diabetic corpulent rats.

1. Groups of lean, obese, and obese-non-insulin-dependent diabetic LA/N-cp and SHR/N-cp rats were administered the a-glucosidase inhibitor Miglitol (150 mg/kg diet, ad libitum) from 8 until 15 weeks of age. 2. Phenotype effects (obese greater than lean) were present for weight gain, adiposity, serum glycemic and lipid parameters, and for liver glucokinase, glucose-6-phosphate dehydrogenase, and malic enzyme activity. Miglitol treatment was associated with improvements in glucokinase and malic enzyme in both strains, and in improvements in glycemic parameters in obese rats. 3. These results are consistent with variable improvements in glycemic control and insulin action following low dose Miglitol treatment, and indicate that indirect effects of the drug on insulin sensitivity in peripheral tissues and on glucoregulatory enzymes may contribute to the glycemic improvements observed with this drug, while greater dosages or longer treatment may be required to observe comparable improvements in adiposity or plasma lipid profiles.

1-Deoxynojirimycin↗

Is insulin detemir able to favor a lower variability in the action of injected insulin in diabetic subjects?

Insulin treated diabetic patients have often to contend with variability in the action of injected insulin and to some unpredictibility in glycemic control. The variability in blood glucose control seems particularly important with long-acting insulins. Insulin detemir belongs to a new class of non-crystalline form of long-acting insulin analogs. Absorption of insulin detemir is dependent on neither appropriate resuspension before injection and dissolution of crystals in the subcutaneous tissue, as is the case for NPH insulin, nor on formation and dissolution of microprecipitates, as is the case for insulin glargine. In euglycemic glucose clamp studies, insulin detemir was associated with significantly less within-subjects variability for the pharmacodynamic endpoints than both NPH insulin and insulin glargine. Three, up to 6 months trials, carried out in patients with type 1 diabetes have shown that the day-to-day within-subject variations in plasma glucose were significantly lower with insulin detemir than with human NPH insulin. Similar results have been reported in patients with type 2 diabetes. Nightly 8-h plasma glucose recordings showed a smoother and more stable profile with insulin detemir than with NPH insulin. In patients with type 1 diabetes the combination of insulin detemir with mealtime insulin aspart, a fast-acting insulin analog, provides a smoother and more stable profile with lower post-prandial plasma glucose levels that the combination of NPH insulin with regular human insulin before each meal. In several trials, the risk of hypoglycemia, particularly of nocturnal hypoglycemia, was significantly lower with insulin detemir than with NPH insulin. In conclusion insulin detemir offers a better reproducibility as compared with other basal insulins, reduces the risk of hypoglycemia, and may lead the patients to titrate their insulin doses more easily and therefore to achieve more often glycemic objectives. The combination of rapid- and long-acting insulin analogs reproduces a more physiological insulin secretion and thereby reduces the risk of hypoglycemia and improves the overall 24-h glycemic profile.

Blood Glucose↗

Predictors of glycemic control on insulin pump therapy in children and adolescents with type I diabetes.

OBJECTIVE: To determine variables predictive of glycemic control in a large population of pediatric patients with type 1 diabetes on continuous subcutaneous insulin infusion (CSII). METHODS: Charts of patients on CSII for > or =1 year were reviewed. "Good" control was a priori defined as HbA1c < or =9% in patients under 12 years of age, and < or =8% in patients over 12 years. RESULTS: Ninety-three patients were identified (57 girls and 36 boys). Their mean age at pump start was 11.6+/-3.1 years with duration of diabetes of 4.7+/-3.1 years. Average time on pump therapy was 2.4+/-0.8 years. HbA1C decreased from 8.7+/-0.9% prior to pump therapy to 8.3+/-0.6% while on CSII (p < 0.01). Despite analysis of a large number of possible predictors, only number of basal rates (4.4 versus 3.4) and younger age (10.0 years versus 13.1 years) correlated with good control. CONCLUSION: Only younger age and use of more basal rates were predictive of good diabetes control in children using CSII. Decisions regarding which pediatric patients are most appropriate for CSII must continue to be individualized.

Adolescent↗

Macular recovery time, diabetic retinopathy, and clinical variables after 7 years of improved glycemic control.

Effects of long-term improved glucose control on neurosensory retinal function are investigated. Changes in macular recovery of nyctometry (photostress) are assessed in 45 insulin-dependent diabetic patients between study start and after 7 years prospective follow-up (the Oslo Study). Intensified insulin treatment improved glycosylated hemoglobin (HbA1) from 11.7 +/- 2.2% at start to a 7-year cumulative mean of 9.5 +/- 1.5% (p less than 0.0001). Improved macular recovery performance was observed in patients with 7-year mean HbA1 below 10%, compared to a worsening in those above 10% (p less than 0.001-0.02), and non-proliferative retinopathy progressed less in those with HbA1 below 10%, than in those above (p less than 0.01). Macular recovery at study start did not predict progression or outcome of retinopathy 7 years later. Intraocular pressure fell during the 7 years (p less than 0.001) and was cross-sectionally negatively correlated to macular recovery at the 7-year end-point (p less than 0.001-0.002). Macular recovery was not related to age, duration of diabetes, systemic blood pressure, or urinary albumin excretion level. The study indicates that severity of retinopathy, glycemic control and intraocular pressure are interesting covariants to neurosensory dysfunction in diabetes. Furthermore, the study suggests a critical level of long-term blood glucose or retinopathy, or both, above which neurosensory function of macular recovery is significantly reduced.

Adult↗

Adequacy of glycemic control in hemodialysis patients with diabetes.

OBJECTIVE: We sought to measure the prevalence of inadequate glycemic control in prevalent hemodialysis patients with diabetes and to examine independent predictors of inadequate glycemic control in these patients. RESEARCH DESIGN AND METHODS: This is a cross-sectional study of prevalent hemodialysis patients with diabetes in southeastern Ontario (n = 100). Data were collected by chart review and interview. The outcome variable was inadequate glycemic control defined as HbA1c (A1C) >0.07. Other measured variables were diabetes type, diabetes duration, diabetes physician, blood glucose monitoring, diabetes medications, BMI, time on dialysis, and other demographic, clinical, and laboratory variables. RESULTS: Fifty-four patients had A1C >0.07. In bivariate analysis, these patients had a longer diabetes duration (23.6 vs. 14.7 years, P < 0.001), higher proportion with insulin use (81.5 vs. 58.7%, P = 0.012), higher proportion with microvascular complications (66.7 vs. 43.5%, P = 0.017), and lower erythropoietin (EPO) dose (7.0 vs. 11.9 x 10(3) units/week, P < 0.01) than patients with adequate glycemic control. There was no difference between the two groups in terms of macrovascular complications (59.3 vs. 65.2%, P = 0.54). In multiple logistic regression controlling for age and diabetes type, the diabetes duration (odds ratio 1.09 [95% CI 1.04-1.15], P < 0.001), EPO dose (0.90 [0.85-0.97], P < 0.01), and blood glucose monitoring (10.06 [1.03-98.74], P = 0.05) were the only significant independent predictors of A1C >0.07. CONCLUSIONS: A high proportion of hemodialysis patients with diabetes had inadequate glycemic control, particularly those with longstanding disease. Patients with inadequate glycemic control had a significantly higher burden of microvascular complications.

Adult↗

Prediction of glucose and insulin responses of normal subjects after consuming mixed meals varying in energy, protein, fat, carbohydrate and glycemic index.

To see if both the amount and source of carbohydrate consumed determined postprandial glucose and insulin responses of mixed meals, eight nondiabetic subjects took five different mixed meals containing variable energy (1650-2550 kJ), fat (8-24 g), protein (12-25 g) carbohydrate (38-104 g) and glycemic index (43-99). Incremental glucose and insulin responses for the five meals varied over a 2.3-fold range. Amount of carbohydrate alone was not significantly related to the mean glucose and insulin responses. However, using previously derived equations, amount of carbohydrate and glycemic index explained approximately 90% of the variability of the observed mean glucose and insulin responses (P = 0.01). We conclude that both amount and source of carbohydrate determine the glucose and insulin responses of lean, young, nondiabetic subjects after different mixed meals with variable glycemic index. Variation in protein and fat intake, over the range tested here, appears to have a negligible effect on postprandial glucose and insulin.

Adult↗

Role of height and glycosylated hemoglobin in abnormal nerve conduction in pediatric patients with type I diabetes mellitus after 4-9 yr of disease.

OBJECTIVE: To determine the role of height and glycosylated hemoglobin in abnormal nerve conduction in pediatric patients with insulin-dependent (type I) diabetes mellitus. RESEARCH DESIGN AND METHODS: Sixty-six pediatric patients (aged 6.3-18.2 yr) with a duration of diabetes from 4 to 8.5 yr but free of clinical neuropathy were evaluated for abnormal nerve conduction. RESULTS: Mean HbA1 values for 1 and 2 yr before study were available. Electroneurographic findings were significantly different from control subjects in upper and lower extremities and included all five measured velocities, three sensory latencies, and one amplitude. Stepwise regression analysis identified an adverse effect of height on latency (5 of 6) and of mean HbA1 concentration on decreasing velocity (4 of 5). The data analysis from 52 patients who were restudied and who had a duration of diabetes from 5.3 to 9.6 yr confirmed that all velocity values slowed; one of five values did so significantly. The coefficients associated with mean HbA1 concentration usually increased in both upper- and lower-extremity velocity analyses at the follow-up examination. The change in peroneal motor velocity between the first and last examinations was significantly related to the increasing time interval between examinations. CONCLUSIONS: Prospective evaluation of nerve conduction parameters in pediatric patients with diabetes should include both height (the most significant independent variable in latency analysis) and mean glycemic control (the most consistent variable in velocity analyses) as variables in the assessment of the natural history of evolving peripheral neuropathy.

Body Height↗

Racial and ethnic differences in glycemic control of adults with type 2 diabetes.

OBJECTIVE: To evaluate glycemic control in a representative sample of U.S. adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged > or = 20 years. Information on medical history and treatment of diabetes was obtained to determine those who had been diagnosed with type 2 diabetes by a physician before the survey (n = 1,480). Fasting plasma glucose and HbA1c were measured, and the frequencies of sociodemographic and clinical variables related to glycemic control were determined. RESULTS: A higher proportion of non-Hispanic blacks were treated with insulin and a higher proportion of Mexican Americans were treated with oral agents compared with non-Hispanic whites, but the majority of adults in each racial or ethnic group (71-83%) used pharmacologic treatment for diabetes. Use of multiple daily insulin injections was more common in whites. Blood glucose self-monitoring was less common in Mexican Americans, but most patients had never self-monitored. HbA1c values in the nondiabetic range were found in 26% of non-Hispanic whites, 17% of non-Hispanic blacks, and 20% of Mexican Americans. Poor glycemic control (HbA1c > 8%) was more common in non-Hispanic black women (50%) and Mexican-American men (45%) compared with the other groups (35-38%), but HbA1c for both sexes and for all racial and ethnic groups was substantially higher than normal levels. Those with HbA1c > 8% included 52% of insulin-treated patients and 42% of those taking oral agents. There was no relationship of glycemic control to socioeconomic status or access to medical care in any racial or ethnic group. CONCLUSIONS: These data indicate that many patients with type 2 diabetes in the U.S. have poor glycemic control, placing them at high risk of diabetic complications. Non-Hispanic black women, Mexican-American men, and patients treated with insulin and oral agents were disproportionately represented among those in poor glycemic control. Clinical, public health, and research efforts should focus on more effective methods to control blood glucose in patients with diabetes.

Adult↗

Effects of two different somatostatin analogs on glucose tolerance in acromegaly.

Impaired glucose tolerance is present in many acromegalic patients and treatment with somatostatin analogs has variable effects on glycemic control. The aim of this study was to compare the effects of 2 somatostatin analogs on glucose metabolism, lanreotide slow release (L-SR) and octreotide long acting release (O-LAR), in 10 patients with acromegaly (2 of whom with overt Type 2 diabetes mellitus). Glucose and insulin levels in fasting conditions and in response to OGTT, evaluated as AUC, insulin resistance (IR) evaluated by homeostatic model assessment (HOMA-IR), glycosylated hemoglobin (HbA1c), GH, IGF-I, were assessed during L-SR and O-LAR treatment. Mean fasting glucose, glucose response to OGTT and HbA1c levels in 8 non-diabetic patients did not significantly change after L-SR therapy while they all increased after O-LAR treatment (p<0.05 vs baseline and L-SR). Mean HOMA-IR values calculated in acromegalic patients before medical therapy were higher than in normal subjects (p<0.005) and showed a significant decrease during both treatments (p<0.05). In the 2 diabetic acromegalic patients a worsening in glucose metabolism was observed during O-LAR treatment but not during L-SR. GH and IGF-I levels significantly decreased with both drugs and normalized respectively in 38% and 12% with L-SR, 50% and 25% with O-LAR. In conclusion, both drugs decreased IR in acromegalic patients; O-LAR seems to be more detrimental to glucose metabolism than L-SR, despite being more effective in reducing GH and IGF-I levels.

Acromegaly↗

Insulin administration via liposomes.

Liposomes have been used in insulin therapy as a means to selectively target insulin to the liver, enhance oral absorption of insulin, and prolong insulin action. Liposomes are an effective means of delivering insulin specifically to hepatocytes. The usefulness of hepatically targeted liposomes in the treatment of diabetes is restricted due to the requirement that they be given intravenously, the dilute concentration of insulin present in liposomal preparations, and the cost associated with liposome production. Encapsulating insulin in liposomes results in enhanced oral absorption of insulin. The high doses of liposome-entrapped insulin required perorally, coupled with extreme variability in the glycemic response to peroral liposomes, limits the value of peroral liposomal insulin as a viable diabetic therapy. Insulin action can be sustained via encapsulation of insulin in liposomes given subcutaneously. Most insulin appears to remain at the injection site, and the presence of a lipid matrix for subcutaneous insulin delivery raises concerns over enhanced antigenicity of liposomal insulin given subcutaneously. Viewed in the light of the limitations outlined above, the contribution of liposomal insulin to understanding and treatment of diabetes mellitus will probably be via use of hepatically targeted liposomes as a pharmacological probe to decipher the role of the liver in the metabolic complications associated with diabetes mellitus.

Diabetes Mellitus, Type 1↗

Dyslipidemia in type II diabetes. Implications for therapeutic intervention.

Cardiovascular disease, and in particular ischemic heart disease, is the principal cause of morbidity, functional disability, and mortality in patients with non-insulin-dependent (type II) diabetes. The main risk factors for the macrovascular complications of diabetes are dyslipidemia, hypertension, and cigarette smoking. Although degree of hyperglycemia is a risk factor for microvascular complications, it is not a prominent risk factor for macrovascular complications. Nevertheless, there are theoretical reasons for believing that glycemic control could lower cardiovascular risk. For example, glycemic control may both improve clearance and suppress hepatic overproduction of very-low-density lipoprotein. Moreover, there is direct empirical evidence that improved glycemic control can favorably alter lipid profiles in type II diabetic patients. Despite this, the only clinical trial that has assessed cardiovascular mortality as an end point in diabetic subjects (i.e., the University Group Diabetes Program) failed to demonstrate a benefit of glycemic control. In this study, the insulin-variable group, which achieved sustained glycemic control relative to the placebo group, had essentially the same cardiovascular mortality as the latter group. All of the conventional lipid-lowering agents have been shown to produce favorable changes in lipid profiles in diabetic subjects. However, the optimum regimen remains to be defined. Metabolic differences between diabetic and nondiabetic subjects mean that the optimum lipid-lowering regimens for the two categories of patients may differ. For example, nicotinic acid, which is a powerful lipid-altering drug, may worsen glucose intolerance. The characteristic lipid abnormalities in type II diabetic subjects are hypertriglyceridemia and low high-density lipoprotein cholesterol, not hypercholesterolemia. Although the role of hypertriglyceridemia as a cardiovascular risk factor in the general population has been questioned, there is evidence that this lipid abnormality may play a stronger role in diabetic subjects. For all of the above reasons, there is an urgent need for large-scale clinical trials assessing cardiovascular end points and testing various strategies of improving lipid profiles in diabetic subjects, particularly given the fact that all of the current generation of lipid-lowering trials have systematically excluded diabetic patients.

Blood Glucose↗

The glycemic index.

Different starchy foods produce different glycemic responses when fed individually, and there is evidence that this also applies in the context of the mixed meal. Methods of processing, and other factors unrelated to the nutrient composition of foods may also have major effects on the glycemic response. The reason for differences in glycemic response appears to relate to the rate at which the foods are digested and the many factors influencing this. The glycemic index (GI) is a system of classification in which the glycemic responses of foods are indexed against a standard (white bread). This allows the results of different investigators to be pooled. GI values also depend upon a number of nonfood-related variables. The method of calculation of the glycemic response area is most important, but the method of blood sampling and length of time of studies also may have effects. Variability of glycemic responses arises from day-to-day variation in the same subject and variation between different subjects. There is less variability between the GI values of different subjects than there is within the same subject from day to day. Therefore, the mean GI values of foods are independent of the glucose tolerance status of the subjects being tested. Potentially clinically useful starchy foods producing relatively flat glycemic responses have been identified, including legumes, pasta, barley, bulgur, parboiled rice and whole grain breads such as pumpernickel. Specific incorporation of these foods into diets have been associated with reduced blood glucose, insulin, and lipid levels. Low-GI foods may influence amino acid metabolism although the implications of these are unknown. In addition, low GI foods increase colonic fermentation. The physiologic and metabolic implications of this relate to increased bacterial urea utilization, and to the production and absorption of short chain fatty acids in the colon. The application of the GI to therapeutic diets should be in the context of the overall nutrient composition of the diet. High-fat or high-sugar foods may have a low GI, but it may not be prudent to recommend these foods solely on the basis of the GI. It is therefore suggested that the most appropriate use of the GI is to rank the glycemic effects of starchy foods which would already have been chosen for possible inclusion in the diet on the basis of their nutritional attributes, i.e. low-fat, unrefined carbohydrate.

Blood Glucose↗

Daily activity level buffers stress-glycemia associations in older sedentary NIDDM patients.

Examined glycemic associations with medical variables, activity, daily stress, and mood state in 72 older patients with non-insulin-dependent diabetes mellitus (NIDDM). On three occasions over a 2-week observation period, subjects provided measures of everyday life stress, negative mood state, and daily activities. At the end of this period, fructosamine was assayed to measure glycemic control throughout the assessment period. After controlling for medical variables (age, illness duration, body mass index, caloric intake, and activity) and the main effects of psychological factors (stress; anxious, angry, and depressed mood states), stress interacted with activity such that glycemic elevation was positively associated with stress for subjects below the activity median but not for those above the median. This was unattributable to any overall activity-related differences in fructosamine, stress, or mood. None of the mood states interacted with activity. The findings suggest that extremely low levels of activity may strengthen life stress-glycemia associations in NIDDM.

Activities of Daily Living↗

Quality of life, health status and clinical outcomes in Type 2 diabetes patients.

This study examines relationships between patient reported outcomes (PROs) and clinical outcomes in Type 2 diabetes mellitus (T2DM). Patients at the outpatient clinics of a university hospital completed measures of generic health status (SF-12), diabetes-specific quality of life (Audit of Diabetes Dependent Quality of Life - ADDQoL), and depressive symptoms (Center for Epidemiologic Studies Depression - CES-D). Patient reported data were merged with a retrospective collection of clinical and utilization data, including HbA1C, from electronic medical records. A Charlson comorbidity score, diabetes complications score, BMI, and total number of ER and hospital visits were calculated. Usable response rate was 44.3% (n = 385). Patients were dichotomized into glycemic control levels based on the ADA recommended A1C level < 7.0, vs. >or= 7.0. The ADDQoL, PCS-12, and MCS-12 scores were separately examined as dependent variables using hierarchical regression models, with glycemic control as the primary explanatory variable, and controlling for demographics and clinical variables including comorbidities and complications. Glycemic control was not a significant predictor in any regression model. Obesity was a significant predictor leading to poorer PCS-12 and MCS-12 scores, while depressive symptoms significantly resulted in lower PCS-12, MCS-12 and ADDQoL scores. These and other factors related to self-management behaviors may contribute to a greater understanding of how to intervene with patients with T2DM. The use of such PROs alongside biomedical measures such as A1C is recommended.

Aged↗

Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics.

We tested the hypothesis that during decrements in plasma glucose concentration, symptoms of hypoglycemia may occur at higher glucose concentrations in patients with poorly controlled insulin-dependent diabetes mellitus than in persons without diabetes. Symptoms of hypoglycemia and counterregulatory neuroendocrine responses were quantified during hypoglycemic and euglycemic clamp studies in eight patients with insulin-dependent diabetes mellitus selected because their hemoglobin A1 levels were above 10 percent. These data were compared with similar observations in 10 nondiabetic subjects studied previously. Glycemic thresholds--the plasma glucose concentrations during each hypoglycemic clamp study at which a given symptom or biochemical measurement first exceeded its 95 percent confidence interval determined in the euglycemic clamp studies--were calculated for each variable. The mean (+/- SE) glycemic threshold for the symptoms of hypoglycemia was 4.3 +/- 0.3 mmol per liter (78 +/- 5 mg per deciliter) in patients with poorly controlled diabetes--significantly higher (P less than 0.001) than the value of 2.9 +/- 0.1 mmol per liter (53 +/- 2 mg per deciliter) in subjects without diabetes. The mean glycemic thresholds for growth hormone, epinephrine, and cortisol secretions were not significantly different in the two groups. Thus, during decreases in the plasma glucose concentration, patients with poorly controlled insulin-dependent diabetes mellitus may experience symptoms of hypoglycemia at higher plasma glucose concentrations than persons without diabetes. The mechanism underlying this observation remains to be defined.

Adult↗

Randomized controlled clinical trial of glargine versus ultralente insulin in the treatment of type 1 diabetes.

OBJECTIVE: Multiple daily insulin injection programs are commonly accompanied by considerable glycemic variation and hypoglycemia. We conducted a randomized crossover design clinical trial to compare glargine with ultralente insulin as a basal insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS: To determine whether the use of glargine insulin as a basal insulin would result in a comparable HbA1c and less glycemic variation and hypoglycemia than ultralente insulin, 22 individuals (aged 44 +/- 14 years [+/-SD], 55% men) with type 1 diabetes who were experienced with multiple daily insulin injections and had an HbA1c of <7.8% were randomized in a crossover design to receive either glargine or ultralente as the basal insulin for 4 months. Aspart insulin was used as the prandial insulin. Physicians providing insulin dose adjustment advice were masked to the type of basal insulin. RESULTS: Treatment with glargine resulted in lower mean HbA1c (6.82 +/- 0.13 vs. 7.02 +/- 0.13, difference: 0.2 +/- 0.08, P = 0.026), less nocturnal variability (plasma glucose 49.06 +/- 4.74 vs. 62.36 +/- 5.21 mg/dl, P = 0.04), and less hypoglycemia (24.5 +/- 2.99 vs. 31.3 +/- 4.04 events, P = 0.05), primarily due to less daytime hypoglycemia (P = 0.002). On the other hand, serious hypoglycemia and average glucose concentration measured with continuous subcutaneous glucose monitoring did not differ. CONCLUSIONS: We conclude that while use of either ultralente or glargine as a basal insulin can result in excellent glycemic control, treatment with glargine is associated with slightly but significantly lower HbA1c and less nocturnal glycemic variability and hypoglycemia.

Adult↗