insulin-glargine and Glucose-Intolerance

The relationship between diabetes and pancreatic cancer is complex. Diabetes or impaired glucose tolerance is present in more than 2/3rd of pancreatic cancer patients. Epidemiological studies have consistently shown a modest increase in the risk of pancreatic cancer in type 2 diabetes, with an inverse relationship to duration of disease. Additionally, recent studies suggest that anti-diabetic medications may modulate the risk of pancreatic cancer in type 2 diabetes. Subjects >50 years of age with new onset diabetes are at higher risk of having pancreatic cancer. However, to screen new-onset diabetes for pancreatic cancer, additional markers are needed that can distinguish pancreatic cancer-associated diabetes from type 2 diabetes.

Topics: Age Factors; Body Mass Index; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Early Detection of Cancer; Evidence-Based Medicine; Global Health; Glucose Intolerance; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Meta-Analysis as Topic; Metformin; Obesity; Pancreatic Neoplasms; Prevalence; Risk Assessment; Risk Factors

The presence of islet autoantibodies and islet reactive T cells (T+) in adults with established type 2 diabetes (T2D) have been shown to identify those patients with more severe β-cell dysfunction. However, at what stage in the progression toward clinical T2D does islet autoimmunity emerge as an important component influencing β-cell dysfunction? In this ancillary study to the Restoring Insulin SEcretion (RISE) Study, we investigated the prevalence of and association with β-cell dysfunction of T+ and autoantibodies to the 65 kDa glutamic acid decarboxylase antigen (GADA) in obese pre-diabetes adults with impaired glucose tolerance (IGT) and recently diagnosed treatment naïve (Ndx) T2D. We further investigated the effect of 12 months of RISE interventions (metformin or liraglutide plus metformin, or with 3 months of insulin glargine followed by 9 months of metformin or placebo) on islet autoimmune reactivity. We observed GADA(+) in 1.6% of NdxT2D and 4.6% of IGT at baseline, and in 1.6% of NdxT2D and 5.3% of IGT at 12 months, but no significant associations between GADA(+) and β-cell function. T(+) was observed in 50% of NdxT2D and 60.4% of IGT at baseline, and in 68.4% of NdxT2D and 83.9% of IGT at 12 months. T(+) NdxT2D were observed to have significantly higher fasting glucose (

Topics: Autoantibodies; Autoantigens; Autoimmunity; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Glargine; Islets of Langerhans; Liraglutide; Metformin; T-Lymphocytes

Pediatric type 2 diabetes prevalence is increasing, with β-cell dysfunction key in its pathogenesis. The RISE Pediatric Medication Study compared two approaches-glargine followed by metformin and metformin alone-in preserving or improving β-cell function in youth with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes during and after therapy withdrawal.. Ninety-one pubertal, overweight/obese 10-19-year-old youth with IGT (60%) or type 2 diabetes of <6 months duration (40%) were randomized to either 3 months of insulin glargine with a target glucose of 4.4-5.0 mmol/L followed by 9 months of metformin or to 12 months of metformin alone. β-Cell function (insulin sensitivity paired with β-cell responses) was assessed by hyperglycemic clamp at baseline, 12 months (on treatment), and 15 months (3 months off treatment).. No significant differences were observed between treatment groups at baseline, 12 months, or 15 months in β-cell function, BMI percentile, HbA. In youth with IGT or recently diagnosed type 2 diabetes, neither 3 months of glargine followed by 9 months of metformin nor 12 months of metformin alone halted the progressive deterioration of β-cell function. Alternate approaches to preserve β-cell function in youth are needed.

Topics: Adolescent; Age Factors; Blood Glucose; Child; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Glargine; Insulin Resistance; Insulin-Secreting Cells; Male; Metformin; Young Adult

Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors.. Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years).. Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group.. In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Fibrinolysis; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Risk Factors; Sweden; Time Factors; Tissue Plasminogen Activator; Treatment Outcome; von Willebrand Factor

As glycaemia and the incidence of microvascular diabetes complications follow a log-linear relationship, it becomes increasingly difficult to demonstrate a microvascular benefit of glucose-lowering when the HbA1c level is close to normal.. The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial randomised 12,537 people with diabetes, impaired glucose tolerance or impaired fasting glucose to receive standard glycaemic care or standard care with the addition of basal insulin glargine (A21Gly,B31Arg,B32Arg human insulin), targeting a fasting plasma glucose level ≤5.3 mmol/l. Microvascular outcomes during a median follow-up of 6.2 years were examined in participants whose baseline HbA1c was above or below the median of 6.4% (46.4 mmol/mol).. Allocation to the insulin glargine group reduced the incidence of the primary microvascular composite outcome of kidney and eye disease in participants whose baseline HbA1c level was ≥6.4% (46.4 mmol/mol; HR 0.90 [95% CI 0.81, 0.99]) but not in participants with a lower baseline HbA1c (HR 1.07 [95% CI 0.95, 1.20]; p value for interaction 0.031). In people whose baseline HbA1c level was ≥6.4% (46.4 mmol/mol), the median post-randomisation change in HbA1c was -0.65% (interquartile range -0.16, -0.91%) after allocation to insulin glargine and -0.33% (-0.83, 0.13%) after allocation to standard care (median HbA1c difference 0.33%; p < 0.0001). A smaller median difference of 0.22% was noted in people whose baseline HbA1c was <6.4% (p < 0.0001).. In patients with dysglycaemia, intervention targeting normal fasting glucose levels reduced HbA1c and attenuated the risk of microvascular outcomes in participants with a baseline HbA1c level ≥6.4% (46.4 mmol/mol). A neutral effect was seen in those with a lower baseline HbA1c level.. ClinicalTrials.gov NCT00069784.

Topics: Aged; Albuminuria; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

Early stages of glucose metabolism impairment are a period at risk in the long-term prognosis of cystic fibrosis (CF). Slow-release synthetic insulin glargine can be a therapeutic tool in this metabolic condition.. In this phase 3 multicenter, controlled, two-arm, randomized clinical study, glargine was administered up to a dosage of 0.15 U/kg/die for a period of 18 months. Primary endpoint was the improvement of nutritional status [body mass index (BMI) Z score], while glucose tolerance [hemoglobin A1c (HbA1C) and respiratory function (FEV1 predicted] improvement were the secondary endpoints.. Thirty-four subjects (18 in the glargine arm and 16 in the control arm) were evaluated. Adherence to insulin treatment was excellent. No significant adverse events were reported. There were no significant differences in BMI, HbA1C and FEV1 values between the two groups nor within groups, except for HbA1C improvement in the glargine arm at month +18 (p = 0.04).. Glargine treatment was well accepted and tolerated. No real efficacy in improving clinical and glycometabolic conditions was demonstrated. Further studies are necessary to test glargine at higher dosage and for a longer follow-up period.

Topics: Adolescent; Adult; Body Mass Index; Child; Cystic Fibrosis; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Lung; Male; Middle Aged; Patient Compliance; Young Adult

The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown.. In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here.. During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups.. Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Topics: Aged; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fatty Acids, Omega-3; Female; Follow-Up Studies; Glucose Intolerance; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Intention to Treat Analysis; Male; Middle Aged; Proportional Hazards Models; Treatment Failure; Triglycerides

The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.. We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups.. The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97).. When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fasting; Fatty Acids, Omega-3; Female; Follow-Up Studies; Glucose Intolerance; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Intention to Treat Analysis; Male; Middle Aged; Proportional Hazards Models; Triglycerides

Diabetes increases morbidity and mortality in cystic fibrosis (CF) patients, but several studies indicate that also prediabetic status may have a potential impact on both nutrition and lung function.. To evaluate the effect of glargine on the clinical course in CF patients with early glucose derangements.. CF population was screened for glucose tolerance. CF patients with age >10 yr were screened with fasting hyperglycemia (FH). CF patients with age >10 yr without FH and those with age <10 yr with occasional FH were evaluated for glucose abnormalities on the basis of oral glucose tolerance test and/or continuous glucose monitoring system. All CF patients with glucose derangements were enrolled in an open clinical trial with glargine. Body mass index (BMI) z-score, forced expiratory volume in the first second (FEV(1)), number of acute pulmonary exacerbations and hemoglobin A1c, were as outcome measures at baseline and after 1 yr of treatment.. After 12 months of therapy, BMI z-score improved only in patients with baseline BMI z-score less than -1 (p = 0.017). An 8.8% increase in FEV(1) (p = 0.01) and 42% decrease in the number of pulmonary exacerbations (p = 0.003) were found in the whole group compared with previous 12 months of therapy.. Glargine could represent an innovative strategy to prevent lung disease progression in CF patients with early glucose derangements. Larger controlled trials are needed to better clarify the effects of insulin on clinical status in CF patients with early glucose derangements.

Topics: Adolescent; Body Mass Index; Child; Cystic Fibrosis; Diabetes Mellitus; Forced Expiratory Volume; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Growth; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Lung Diseases; Spirometry; Treatment Outcome

Determine if pre-emptive daily insulin glargine surpasses regular insulin when needed for glycaemic control after cardiac surgery.. Prospective, randomized study of 43 patients (scheduled for coronary artery bypass grafting) with preoperatively diagnosed diabetes (DM) or pre-DM. Lantus group received insulin glargine daily from start of surgery while Actrapid group received regular insulin (sliding scale) when needed (plasma glucose (P-glu)>10 mmol/l). Primary endpoint was percent of pre- and post-prandial P-glu values within Target Intervals: Pre-prandial P-glu: 4.5-7 mmol/l; post-prandial P-glu: 4.5-9 mmol/l. Study period 1-4 days after surgery. Tissue glucose was also measured continuously.. More than twice as many P-glu values were within Target Interval for Lantus patients as compared with Actrapid patients (p<0.001). One of 504 timed measurements was <4 mmol/l. Area under the curve for glucose>7 mmol/l was reduced by 61% by Lantus (p<0.001).. The routine protocol with pre-emptive glargine insulin studied here provides a major improvement in glycaemic control with a minimal incidence of hypoglycaemia and without an excessive increase in nursing burden.

Topics: Aged; Blood Glucose; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus; Drug Administration Schedule; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Pilot Projects; Prediabetic State; Prospective Studies; Time Factors; Treatment Outcome

People with early type 2 diabetes and pre-diabetes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) are at risk of hyperglycaemia-related complications, including cardiovascular disease. Insulin, traditionally reserved as late treatment in type 2 diabetes, may also be a useful therapy in this population. We examined the short-term efficacy and tolerability of insulin glargine (glargine) in individuals with early or pre-type 2 diabetes.. In this multicentre, double-blind, placebo-controlled, randomized, parallel group, 12-day study, subjects with IGT/IFG (n=9), newly diagnosed type 2 diabetes (n=9) or normal glucose tolerance (n=3) (confined to a clinical research unit taking a prescribed diet) were randomized to once-daily glargine (n=16) or placebo (saline; n=5) at bedtime. Dose was titrated to achieve target fasting blood glucose (FBG) 80-95 mg/dL.. Over the treatment period, mean FBG decreased in glargine-treated subjects (from 100.0+/-18.8 to 85.6+/-18.4 mg/dL), but was unchanged in placebo-treated subjects (from 112.5+/-10.6 to 111.3+/-17.5 mg/dL). Mean eight-point blood glucose value decreased by 9.7 mg/dL in the glargine group, but increased by 8.1 mg/dL in the placebo group. Mean post-exercise blood glucose was similar before and after glargine treatment, but increased after placebo treatment. Five subjects receiving glargine experienced 16 mild symptomatic hypoglycaemia episodes; however, no hypoglycaemia occurred during exercise. Mean body weight decreased in both the glargine (-0.44 kg) and placebo (-0.25 kg) groups, in line with dietary restrictions.. The results of this pilot study suggest that glargine can be used by people with IFG, IGT or new-onset type 2 diabetes for management of hyperglycaemia with low risk of hypoglycaemia. However titration of insulin in people on dietary restrictions should be more cautious as they may be more prone to hypoglycaemia. Further studies are warranted to determine the clinical benefits of this approach.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Feasibility Studies; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Pilot Projects; Placebos; Prediabetic State; Time Factors; Treatment Outcome

β-Cell dysfunction is central to the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes. Compared with adults, youth have hyperresponsive β-cells and their decline in β-cell function appears to be more rapid. However, there are no direct comparisons of β-cell responses to pharmacological intervention between the two age-groups. The Restoring Insulin Secretion (RISE) Adult Medication Study and the RISE Pediatric Medication Study compared interventions to improve or preserve β-cell function. Obese youth (

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Glargine; Insulin Resistance; Male; Metformin; Middle Aged

The Restoring Insulin Secretion (RISE) Adult Medication Study compared pharmacological approaches targeted to improve β-cell function in individuals with impaired glucose tolerance (IGT) or treatment-naive type 2 diabetes of <12 months duration.. All three active treatments produced on-treatment reductions in weight and improvements in HbA. In adults with IGT or recently diagnosed type 2 diabetes, interventions that improved β-cell function during active treatment failed to produce persistent benefits after treatment withdrawal. These observations suggest that continued intervention may be required to alter the progressive β-cell dysfunction in IGT or early type 2 diabetes.

Topics: Adult; Arginine; B-Lymphocytes; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Liraglutide; Male; Metformin; Middle Aged; Withholding Treatment

To explore the beneficial effects of dapagliflozin and/or insulin glargine on the pancreatic beta cell mass and hepatic steatosis in db/db mice.. Six-week-old db/db mice were assigned to one of four groups: untreated (Placebo), treated with dapagliflozin (Dapa), treated with insulin glargine (Gla), or treated with dapagliflozin and insulin glargine (Dapa+Gla). After 8 weeks of treatment, we determined glucose tolerance, beta cell mass, hepatic lipid content and gene expression.. Glucose tolerance was significantly ameliorated in the three treated groups to the same degree compared with the Placebo group. Immunohistochemical analysis revealed that the pancreatic beta cell mass was significantly maintained in the Dapa and Dapa+Gla groups, but not in the Gla group, compared with the Placebo group (Placebo 2.25 ± 1.44 mg, Dapa 5.01 ± 1.63 mg, Gla 3.79 ± 0.96 mg, Dapa+Gla 5.19 ± 1.78 mg). However, the triglyceride content of the liver was markedly elevated in the Gla group compared with that in the other three groups (Placebo 24.1 ± 11.5 mg, Dapa 30.6 ± 12.9 mg, Gla 128 ± 49.7 mg, Dapa+Gla 54.4 ± 14.1 mg per gram liver). The expression levels of genes related to fatty acid synthesis and lipid storage were significantly upregulated in the Gla group.. Our results showed that beta cell mass was sustained and hepatic steatosis was prevented, after 8 weeks of treatment with either dapagliflozin or dapagliflozin plus insulin glargine, but not with insulin glargine alone, in db/db mice.

Topics: Animals; Benzhydryl Compounds; Fatty Acids; Gene Expression; Glucose Intolerance; Glucosides; Hypoglycemic Agents; Insulin Glargine; Insulin-Secreting Cells; Lipid Metabolism; Liver; Male; Mice; Non-alcoholic Fatty Liver Disease; Sodium-Glucose Transporter 2 Inhibitors; Triglycerides

Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Patient Safety; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

To investigate whether the combination of HbA1c and fasting plasma glucose (FPG) can be used for the diagnosis of diabetes and impaired glucose tolerance (IGT) in people at high risk of cardiovascular disease (CVD).. A cross-sectional study was performed on 2907 people at high risk of cardiovascular events but without a previous diagnosis of diabetes. Optimal cut-off points and the diagnostic potential of FPG, HbA1c, and their combination were determined.. The sensitivity of the usually applied FPG cut-off point of 7.0 mmol/L to diagnose diabetes mellitus was low (59.0%). Receiver operating characteristic (ROC) curve analysis indicated that the optimal cut-off points for the diagnosis of diabetes using FPG and HbA1c were 6.4 mmol/L (sensitivity 75.7%; specificity 77.5%; likelihood ratio 3.37) and 5.9% (41 mmol/mol; sensitivity 68.7%; specificity 67.1%; likelihood ratio 2.09), respectively. To diagnose IGT, the optimal cut-off points for FPG and HbA1c were 6.1 mmol/L (sensitivity 57.1%; specificity 57.9%) and 5.7% (39 mmol/mol; sensitivity 63.8%; specificity 60.3%), respectively. For diabetes, combining cut-off points for FPG and HbA1c identified four categories with likelihood ratios ranging from 5.59 to 0.21, and post-test probabilities between 69.3% and 7.8%. For IGT, likelihood ratios varied between 2.05 and 0.56, whereas post-test probabilities ranged from 84.0% to 58.8%.. Using FPG alone results in the underdiagnosis of glucometabolic abnormalities in people at high risk of CVD. Using an algorithm with both HbA1c and FPG improves the detection of diabetes, but not IGT, and could be easily implemented in patient care.

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Risk Factors; ROC Curve

Diabetes mellitus is an increasing complication of cystic fibrosis (CF), as a result of the improved life expectancy. There is clear association between diabetes and increased morbidity and mortality. Lung function and clinical status deteriorate up to 2-4 yr before the diagnosis of CF-related diabetes (CFRD). The aim of our study was to evaluate the effects, on glucose homeostasis and clinical status, of the early treatment with insulin glargine in CF patients with impaired glucose tolerance (IGT). We selected six subjects with IGT diagnosed at oral glucose tolerance test (OGTT). Median age was 18.12 yr (range 9.2-27.8). Insulin glargine was administered at the median dosage of 0.3 U/kg/day (range 0.2-0.5). After the initial adjustment of the dosage, no patient manifested hypoglycemia during treatment. Median glycosylated hemoglobin (HbA1c) did not show any significant variation during treatment: it was 5.9% at baseline (range 5.5-6.2) and 6.1% (range 5.0-6.7) at the end of follow-up (p=0.496). Median body mass index (BMI) z-score significantly increased during treatment, from -0.95 (range -3.2-+0.6) at baseline to -0.5. (range -3.0-+0.9) at the end of follow-up (p=0.026). Lung function, measured by median forced expiratory volume in the first second (FEV1%), showed a mild but significant improvement during insulin treatment. It was 72.7% at baseline (range 41.5-98.4) and 76.7% (range 42.0-106.8) at the end of follow-up (p=0.027). No significant variation was found between the number of hospitalizations for clinical exacerbation (no./patient/yr) in the last 2 yr before treatment and during follow-up. Median number at baseline was 1.95/patient/yr (range 1-3) and 2.0/patient/yr (range 1-3) at follow-up (p=0.715). Our data seem to indicate that early insulin therapy can be safe, no patient manifested hypoglycemia or other adverse effects during treatment. Insulin is an anabolic hormone implicated in both lipid and protein metabolism. The appearance of IGT out of infections can indicate an early insulin deficiency, with a potential impact on the nutritional and clinical status of the patient, even before the appearance of overt diabetes. Larger controlled trials are necessary to verify if early insulin therapy is able to reduce the deterioration of nutritional status and lung function associated with the onset of IGT.

Topics: Adolescent; Adult; Blood Glucose; Child; Cystic Fibrosis; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Lung; Male; Nutritional Status