H. Hanaire

Incremental value of continuous glucose monitoring when starting pump therapy in patients with poorly controlled type 1 diabetes: The RealTrend study

OBJECTIVE To compare the improvements in glycemic control associated with transitioning to insulin pump therapy in patients using continuous glucose monitoring versus standard blood glucose self-monitoring. RESEARCH DESIGN AND METHODS The RealTrend study was a 6-month, randomized, parallel-group, two-arm, open-label study of 132 adults and children with uncontrolled type 1 diabetes (A1C ≥8%) being treated with multiple daily injections. One group was fitted with the Medtronic MiniMed Paradigm REAL-Time system (PRT group), an insulin pump with integrated continuous subcutaneous glucose monitoring (CGM) capability, with instructions to wear CGM sensors at least 70% of the time. Conventional insulin pump therapy was initiated in the other group (continuous subcutaneous insulin infusion [CSII] group). Outcome measures included A1C and glycemic variability. RESULTS A total of 115 patients completed the study. Between baseline and trial end, A1C improved significantly in both groups (PRT group −0.81 ± 1.09%, P < 0.001; CSII group −0.57 ± 0.94%, P < 0.001), with no significant difference between groups. When the 91 patients who were fully protocol-compliant (including CGM sensor wear ≥70% of the time) were considered, A1C improvement was significantly greater in the PRT group (P = 0.004) (PRT group −0.96 ± 0.93%, P < 0.001; CSII group −0.55 ± 0.93%, P < 0.001). Hyperglycemia parameters decreased in line with improvements in A1C with no impact on hypoglycemia. CONCLUSIONS CGM-enabled insulin pump therapy improves glycemia more than conventional pump therapy during the first 6 months of pump use in patients who wear CGM sensors at least 70% of the time.

Assessment of Patient-Led or Physician-Driven Continuous Glucose Monitoring in Patients With Poorly Controlled Type 1 Diabetes Using Basal-Bolus Insulin Regimens A 1-year multicenter study

OBJECTIVE The benefits of real-time continuous glucose monitoring (CGM) have been demonstrated in patients with type 1 diabetes. Our aim was to compare the effect of two modes of use of CGM, patient led or physician driven, for 1 year in subjects with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes aged 8–60 years with HbA1c ≥8% were randomly assigned to three groups (1:1:1). Outcomes for glucose control were assessed at 1 year for two modes of CGM (group 1: patient led; group 2: physician driven) versus conventional self-monitoring of blood glucose (group 3: control). RESULTS A total of 257 subjects with type 1 diabetes underwent screening. Of these, 197 were randomized, with 178 patients completing the study (age: 36 ± 14 years; HbA1c: 8.9 ± 0.9%). HbA1c improved similarly in both CGM groups and was reduced compared with the control group (group 1 vs. group 3: −0.52%, P = 0.0006; group 2 vs. group 3: −0.47%, P = 0.0008; groups 1 + 2 vs. group 3: −0.50%, P < 0.0001). The incidence of hypoglycemia was similar in the three groups. Patient SF-36 questionnaire physical health score improved in both experimental CGM groups (P = 0.004). Sensor consumption was 34% lower in group 2 than in group 1 (median [Q1–Q3] consumption: group 1: 3.42/month [2.20–3.91] vs. group 2: 2.25/month [1.27–2.99], P = 0.001). CONCLUSIONS Both patient-led and physician-driven CGM provide similar long-term improvement in glucose control in patients with poorly controlled type 1 diabetes, but the physician-driven CGM mode used fewer sensors.

High glycemic variability assessed by continuous glucose monitoring after surgical treatment of obesity by gastric bypass.

BACKGROUND Obesity surgery elicits complex changes in glucose metabolism that are difficult to observe with discontinuous glucose measurements. We aimed to evaluate glucose variability after gastric bypass by continuous glucose monitoring (CGM) in a real-life setting. METHODS CGM was performed for 4.2 ± 1.3 days in three groups of 10 subjects each: patients who had undergone gastric bypass and who were referred for postprandial symptoms compatible with mild hypoglycemia, nonoperated diabetes controls, and healthy controls. RESULTS The maximum interstitial glucose (IG), SD of IG values, and mean amplitude of glucose excursions (MAGE) were significantly higher in operated patients and in diabetes controls than in healthy controls. The time to the postprandial peak IG was significantly shorter in operated patients (42.8 ± 6.0 min) than in diabetes controls (82.2 ± 11.1 min, P = 0.0002), as were the rates of glucose increase to the peak (2.4 ± 1.6 vs. 1.2 ± 0.3 mg/mL/min; P = 0.041). True hypoglycemia (glucose <60 mg/dL) was rare: the symptoms were probably more related to the speed of IG decrease than to the glucose level achieved. Half of the operated patients, mostly those with a diabetes background before surgery, had postprandial glucose concentrations above 200 mg/dL (maximum IG, 306 ± 59 mg/dL), in contrast to the normal glucose concentrations in the fasting state and 2 h postmeal. CONCLUSIONS Glucose variability is exaggerated after gastric bypass, combining unusually high and early hyperglycemic peaks and rapid IG decreases. This might account for postprandial symptoms mimicking hypoglycemia but often seen without true hypoglycemia. Early postprandial hyperglycemia might be underestimated if glucose measurements are done 2 h postmeal.

Usefulness of Acarbose and Dietary Modifications to Limit Glycemic Variability Following Roux-en-Y Gastric Bypass as Assessed by Continuous Glucose Monitoring

BACKGROUND About 70% of the patients operated on for a gastric bypass (Roux-en-Y gastric bypass [RYGB]) suffer from dumping syndrome. In these patients, previous studies have demonstrated a high glycemic variability with hypoglycemia and with altered continuous glucose monitoring (CGM) profiles. The aim of this study was to evaluate the effect of treatment with dietary counseling plus acarbose administration on the symptoms and on the characteristics of the CGM profile. SUBJECTS AND METHODS Eight consecutive patients with dumping syndrome were given dietary counseling for 6 weeks and also treated with acarbose (50-100 mg three times a day). Their symptoms and the features of the CGM were compared before and after treatment. RESULTS The symptoms disappeared in seven patients. There was a significant increase in the time to the interstitial glucose (IG) peak and a reduction in the rate of the IG increase after a meal and in the rate of the IG decrease following the peak. The time below 60 mg/dL was significantly decreased, and the minimal IG value was significantly increased. The maximum and mean IG levels and the time above 140 mg/dL were decreased, but not significantly. Six patients spent more than 1% of the time with IG values below 60 mg/dL before treatment, but after treatment this was reduced to one patient. Before treatment only one patient had an IG level neither below 60 or above 140 mg/dL, and after treatment four patients were in this category. CONCLUSIONS Dietary counseling and acarbose treatment eliminated the symptoms and improved the CGM profile of patients suffering from dumping syndrome after RYGB.

Relationship Between Markers of Insulin Resistance, Markers of Adiposity, HbA1c, and Cognitive Functions in a Middle-Aged Population–Based Sample: the MONA LISA Study

OBJECTIVE To determine the relationship between markers of insulin resistance (fasting insulin and homeostasis model assessment of insulin resistance), markers of adiposity (BMI, waist circumference, and body fat), HbA1c, and cognitive performances in a middle-aged population–based sample free of diabetes. RESEARCH DESIGN AND METHODS Our study sample consisted of 1,172 people aged 35–64 years (49% women), free of diabetes, and recruited between 2005 and 2007 in the MONA LISA survey. Cognitive functions (memory, attention, and processing speed) were evaluated by neuropsychological tests: word-list learning test, digit symbol substitution test (DSST), word fluency test, and Stroop Test. Multiple logistic regressions were used to estimate the relationship between cognitive performance and metabolic markers. We serially adjusted for age, sex, education, and occupational status (model A), additionally for income, smoking, alcohol consumption, sedentarity, and psychotropic substance use (model B), and finally, included variables linked to the metabolic syndrome (hypertension, dyslipidemia, vascular disease, and C-reactive protein) and depression (model C). RESULTS Elevated markers of adiposity were associated with poor cognitive performance in tests evaluating processing speed. The probability of being in the lowest quartile of each test was nearly doubled for participants in the upper quartile of BMI, compared with those in the lowest one [BMI, adjusted odds ratio (OR) 2.18, P = 0.003 (DSST), and OR 2.09, P = 0.005 (Stroop Test)]. High HbA1c was associated with poor cognitive performance in DSST (adjusted OR 1.75, P = 0.037). Waist circumference was linked to poor cognitive performance in men but not in women. CONCLUSIONS Poor cognitive performance is associated with adiposity and hyperglycemia in healthy middle-aged people.

Access of children and adolescents with type 1 diabetes to insulin pump therapy has greatly increased in France since 2001

AIM Insulin pump therapy is an emerging option in the management of type 1 diabetes (T1D), but it often remains unused. For this reason, in 2007, a French national survey was carried out to update the frequency of insulin pump use in the paediatric population compared with a previous survey done in 2001. METHODS The present survey was performed in hospital departments involved in paediatric diabetes management (n = 67) and in adult departments involved in adolescent diabetes management (n = 113). The number of T1D children (age < 18 years) treated in each department, with or without the use of an insulin pump, and the number of insulin pump therapies initiated during the previous year were collected. RESULTS A total of 60 paediatric and 28 adult centres responded, involving 9073 T1D children and adolescents (93% in paediatric departments). Of these patients, 1461 (16%) were treated by insulin pump, 89% of which were managed in paediatric centres. However, pump use was more frequent in adult than in paediatric centres (32% versus 18%, respectively). Also, 38% of insulin pumps were initiated during the year prior to the survey. In addition, in 2001, 140 children were treated with insulin pump in 13 paediatric centres (versus 56 centres in 2007). CONCLUSION The number of centres using insulin pump therapy for diabetic children and the number of children treated by insulin pump were increased fourfold and 10-fold, respectively, from 2001 to 2007, indicating greater access to pump therapy in the French paediatric population. The present survey is still ongoing to evaluate the decision-making criteria that influence the initiation of insulin pump therapy in T1D paediatric patients.

Increased risk of OGTT-induced hypoglycemia after gastric bypass in severely obese patients with normal glucose tolerance

BACKGROUND Hypoglycemic episodes are described after bariatric surgery. OBJECTIVE To report the prevalence of hypoglycemia after a 75 g oral glucose load (OGTT) after Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (LAGB), and to identify predicting factors. SETTING Bariatric surgery referral center. METHODS Prospective cohort of 351 consecutive patients before and 12 months after bariatric surgery, on whom an OGTT was performed. The main outcome measure was postchallenge hypoglycemia (PCHy), defined as a 120 minute plasma glucose value<2.8 mmol/L (50.4 mg/dL). RESULTS Only patients with an RYGB presented with PCHy. It occurred in 23 patients or a prevalence of 10.4% after an RYGB. The OR was 25.5 (95% CI 3.4-191; P<.001) compared with before surgery. Patients with PCHy after surgery had a lower glycated hemoglobin (HbA1c), and a lower 2-hour postchallenge value before surgery. Before surgery, patients with normal glucose tolerance had an increased risk of PCHy after surgery (OR 8.6, 95% CI 2.0-37.6; P< .001). CONCLUSIONS The prevalence of OGTT-induced hypoglycemia is increased 25.5 times, 12 months after an RYGB. This is not observed after a gastric banding.

Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVE™ study in a cohort of French patients with type 1 or type 2 diabetes

AIM PREDICTIVE (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n=1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes. METHODS Patients were prescribed insulin detemir at their physicians discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA(1c), fasting blood glucose and variability of fasting blood glucose) and weight change. RESULTS The incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P<0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA(1c), by -0.6% and -0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by -1.4mmol/L and -1.9mmol/L respectively; and FBG variability, by -0.8mmol/L and -0.3mmol/L, respectively (P<0.0001 for all). CONCLUSION Patients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.

Post-prandial hypoglycemia results from a non-glucose-dependent inappropriate insulin secretion in Roux-en-Y gastric bypassed patients

BACKGROUND After Roux-en-Y gastric bypass (RYGB), hypoglycemia can occur and be associated with adverse events such as intense malaise and impaired quality of life. OBJECTIVE To compare insulin secretion, sensitivity, and clearance between two groups of patients, with or without hypoglycemia, after an oral glucose tolerance test (OGTT 75-g), and also to compare real-life glucose profiles within these two groups. SETTING Bariatric surgery referral center. METHODS This study involves a prospective cohort of 46 consecutive patients who complained of malaise compatible with hypoglycemia after RYGB, in whom an OGTT 75-g was performed. A plasma glucose value of lower than 2.8 mmol/L (50 mg/dl) between 90 and 120 min after the load was considered to be a significant hypoglycemia. The main outcome measures were insulin sensitivity, beta-cell function, and glycemic profiles during the test. Glucose parameters were also evaluated by continuous glucose monitoring (CGM) in a real-life setting in 43 patients. RESULTS Twenty-five patients had plasma glucose that was lower than 2.8 mmol/L between 90 and 120 from the load (HYPO group). Twenty-one had plasma glucose that was higher than 2.8 mmol/L (NONHYPO group). The HYPO patients were younger, had lost more weight after RYGB, were less frequently diabetic before surgery, and displayed higher early insulin secretion rates compared with the NONHYPO patients after the 75-g OGTT, and they had lower late insulin secretion rates. The HYPO patients had lower interstitial glucose values in real life, which suggests that a continuum exists between observations with an oral glucose load and real-life interstitial glucose concentrations. CONCLUSIONS This study suggests that HYPO patients after RYGB display an early increased insulin secretion rate when tested with an OGTT. CGM shows that HYPO patients spend more time below 3.3 mmol/L when compared with NONHYPO patients. This phenotype of patients should be monitored carefully after RYGB.

Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic-euglycaemic clamp

Apelin is a recently identified adipokine known to improve glucose tolerance and insulin sensitivity in murine models. This study was dedicated to the proof of concept that apelin administration also enhances insulin sensitivity in humans.