Combined Pioglitazone and Metformin Treatment Maintains the Beneficial Effect of Short-Term Insulin Infusion in Patients with Type 2 Diabetes: Results from a Pilot Study

Background

The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application.

Methods

This prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5 female, 9 male; age 60 ± 2 years; body mass index 29 ± 3.2 kg/m²; hemoglobin A1c [HbA1c] 7.6 ± 1.1%) with (1) insufficient glycemic control under a dose of metformin ≥1700 mg/day and/or metformin plus additional oral antidiabetes drugs (OADs) and (2) appropriate residual β-cell function. Initially, an inpatient 34 h continuous intravenous insulin infusion was performed, and metformin was given (2x 850 mg/day). Insulin was stopped, and pioglitazone 30 mg/day was added at the second inpatient day. Patients were followed for four months. Efficacy parameters [change of HbA1c, fasting blood glucose [FBG], intact proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP)] were assessed after initial normalization of blood glucose values by intravenous insulin and at the study end point.

Results

During the acute insulin intervention, FBG levels were stabilized in all study subjects. In the following OAD treatment period, five patients showed an improvement of HbA1c > 0.5% [35.7%; seven patients remained stable (50.0%), two patients were nonresponders (14.3%)].Fasting glucose values dropped after insulin infusion (-17.7%; p < .001). This effect was maintained during the consecutive OAD treatment period (glucose +0.3%, not significant (NS); HbA1c -6.0%; p < .05). The initial decrease in fasting intact proinsulin levels was also maintained during the study (end value -41%, p < .05).Improvements in hsCRP values (postinsulin value, -15%, NS; end value -37%; p < .05) and adiponectin values (postinsulin value +15%, NS; end value +128%; p < .001) were demonstrated at end point only after continued glitazone intake.

Conclusions

Our pilot study demonstrated that a beneficial effect of a short-term intravenous insulin application on glycemic control was effectively maintained by pioglitazone/metformin treatment for at least 4 months. In addition, the oral therapy significantly improved cardiovascular risk parameters.     

Determinants of the accuracy of continuous glucose monitoring in non-critically ill patients with heart failure or severe hyperglycemia

Background

The accuracy of continuous glucose monitoring (CGM) in non-critically ill hospitalized patients with heart failure or severe hyperglycemia (SH) is unknown.

Methods

Hospitalized patients with congestive heart failure (CHF) exacerbation (receiving IV or subcutaneous insulin) or SH requiring insulin infusion were compared to outpatients referred for retrospective CGM.

Results

Forty-three patients with CHF, 15 patients with SH, and 88 outpatients yielded 470, 164, and 2150 meter–sensor pairs, respectively. Admission glucose differed (188 versus 509 mg/dl in CHF and SH, p < .001) but not the first sensor glucose (p = .35). In continuous glucose error grid analysis, 67–78% of pairs during hypoglycemia were in zones A+B (p = .63), compared with 98–100% in euglycemia (p < .001) and 98%, 92%, and 99% (p = .001) during hyperglycemia for the CHF, SH, and outpatient groups, respectively. Mean absolute relative difference (MARD) was lower in the CHF versus the SH group in glucose strata above 100 mg/dl, but there was no difference between the CHF and outpatient groups. Linear regression models showed that CHF versus outpatient, SH versus CHF, and coefficient of variation were significant predictors of higher MARD. Among subjects with CHF, MARD was not associated with brain natriuretic peptide or change in plasma volume, but it was significantly higher in subjects randomized to IV insulin (p = .04).

Conclusions

The results suggest that SH and glycemic variability are more important determinants of CGM accuracy than known CHF status alone in hospitalized patients.     

High sensitivity C-reactive protein and cardfiac resynchronization therapy in patients with advanced heart failure

Background The data on the prognostic values of high sensitivity C-reactive protein （hsCRP） levels in patients with advanced symp-tomatic heart failure （HF） receiving cardiac resynchronization therapy （CRT） are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome. Methods A total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF. Results During the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP （〉3 mg/L） prior to CRT was associated with a significant 2.39-fold increase （P=0.006） in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels （–0.5 ± 4.1 mg/L reduction） compared with non-responders （1.7 ± 6.1 mg/L increase, P=0.018）. Com-pared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations （Log-rank P〈0.001）. The echocardio-graphic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high. Conclusions Our findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.     

Postprandial Glycemic Excursions with the Use of a Closed-Loop Platform in Subjects with Type 1 Diabetes: A Pilot Study

Background

The aim of this study was to evaluate the efficacy of a proportional derivative algorithm closed-loop system to control postprandial glucose concentrations in subjects with type 1 diabetes.

Methods

Six subjects treated with continuous subcutaneous insulin infusion received a standardized meal on three days. The first day served as control, the second day as learning experiment for the algorithm, and the third day to compare the closed loop to the control day. Venous blood glucose was measured as reference until 300 min postprandially. The artificial pancreas platform consisted of a subcutaneous continuous glucose monitor (CGM), the GlucoDay^® S (Menarini Diagnostics), two D-Tron+ pumps (Disetronic Medical Systems) for subcutaneous insulin, and glucagon administration connected to a personal computer.

Results

One subject was excluded due to technical failure of the CGM. Two of five subjects were male, mean age was 50.8 years (range 38–60), and mean hemoglobin A1c was 8.7% (range 7.0–12.2). The mean postprandial venous blood glucose concentration of day 1 was 205 mg/dl (range 94–265 mg/dl) compared with 128 mg/dl (range 128–158 mg/dl) on day 3 (p = .14). Percentage of time spent in euglycemia postprandially on day 1 was 31% versus 60% on day 3 (p = .08). Time spent below 3.9 mmol/liter (70 mg/dl) was 19% on day 1 compared with 11% on day 3 (p = 1.0). Time above 10 mmol/liter (180 mg/dl) on day 1 was 60% versus 29% on day 3 (p = .22).

Conclusion

The artificial pancreas provided comparable postprandial glycemic control to usual care.     

Metabolic syndrome vs. its components for prediction of cardiovascular mortality: A cohort study in Chinese elderly adults

Objectives The predictive value of the metabolic syndrome (MetS) for mortality from all-cause and cardiovascular disease (CVD) in the Chinese population is unclear. The aim of this present study was to compare MetS with its individual components as predictors of mortality in Chinese elderly adults. Methods A cohort of 1,535 subjects (994 men and 541 women) aged 50 years or older was selected from employees of a machinery factory in 1994 and followed until 2009. Cox models were used to estimate the hazard ratios (HRs) predicted by MetS according to the harmonized definition and by its individual components. Results The baseline prevalence of MetS was 28.0% in men and 48.4% in women. During a median follow-up of 15 years, 414 deaths occurred, of these, 153 participants died from CVD. Adjusted for age and gender, the HRs of mortality from all-cause and CVD in participants with MetS were 1.47 (95% confidence interval (CI): 1.20–1.80) and 1.96 (95%CI: 1.42–2.72), respectively, compared with those without MetS. Non-significant higher risk of CVD mortality was seen in those with one or two individual components (HR = 1.22, 95%CI: 0.59–2.50; HR = 1.82, 95%CI: 0.91–3.64, respectively), while a substantially higher risk of CVD mortality only appeared in those with 3, 4, or 5 components (HR = 2.81–3.72), compared with those with no components. On evaluating the MetS components individually, we found that, independent of MetS, only hypertension and impaired glucose predicted higher mortality. Conclusions The number of positive MetS components seems no more informative than classifying (dichotomous) MetS for CVD risks assessment in this Chinese cohort.     

Lack of predictive power of plasma lipids or lipoproteins for gestational diabetes mellitus in Japanese women

Aims/Introduction

To determine the diagnostic potential of plasma lipids and apolipoproteins in gestational diabetes mellitus (GDM), we carried out a retrospective cohort study of 1,161 Japanese women at 20–28 weeks of gestation who underwent a glucose challenge test (GCT).

Materials and Methods

A total of 1,161 Japanese women at 20–28 weeks of gestation underwent a GCT. Participants with a positive test (GCT[+]) underwent a subsequent oral glucose tolerance test. Clinical and biochemical parameters were determined and quantification of apolipoproteins (Apo), including ApoB, ApoB48, ApoA-I and ApoC-III, was carried out.

Results

The prevalence of GCT(+; with a 130 mg/dL glucose cut-off) and GDM was 20% and 4%, respectively. There was a trend for increased triglycerides and ApoC-III in GDM(+) participants. However, the difference in plasma triglycerides, ApoC-III or ApoB48 did not reach statistical significance between GDM(+) and GDM(−) women. Values of 1-h glucose (P < 0.001) and fasting glucose (P = 0.002) were significant risk factors for GDM.

Conclusions

Prediction of GDM using only the ApoC-III value is not easy, although triglycerides and ApoC-III were higher in the GDM(+) group. The present findings show no significant difference in plasma lipid levels between women diagnosed with GDM and those with normal glucose tolerance.     

Reduction of postprandial glycemic excursions in patients with type 1 diabetes: a novel human insulin formulation versus a rapid-acting insulin analog and regular human insulin

Background:

Evaluation of postprandial glycemic excursions in patients with type 1 diabetes with three prandial insulins: VIAject™ (Linjeta™), an ultra-fast insulin (UFI); insulin lispro (LIS); and regular human insulin (RHI).

Methods:

After stabilization of preprandial glycemia, 18 patients received a subcutaneous injection with an individualized insulin dose prior to a meal.

Results:

Injection of UFI resulted in a more rapid insulin absorption than with either LIS or RHI (time to half-maximal insulin levels: 13.1 ± 5.2 vs 25.4 ± 7.6 and 38.4 ± 19.5 min; p = .001 vs LIS and p < .001 vs RHI, LIS vs. RHI p < .001). Maximal postprandial glycemia was lower with UFI (0–180 min; 157 ± 30 mg/dl; p = .002 vs RHI) and LIS (170 ± 42 mg/dl; p = .668 vs RHI) than after RHI (191 ± 46 mg/dl; RHI vs LIS p = .008). The difference between maximum and minimum glycemia was smaller with UFI (70 ± 17 mg/dl) than with either RHI (91 ± 33 mg/dl; p = .007 vs UFI) or LIS (89 ± 18 mg/dl; p = .011 vs UFI). Also, the area under the blood glucose profile was lower with UFI than with RHI (0–180 min; 21.8 ± 5.8 vs 28.4 ± 7.6 g·min/dl; p < .001).

Conclusions:

The rapid absorption of UFI results in a reduction of postprandial glycemic excursions.     

Prevalence of sleep abnormalities and their association with metabolic syndrome among Asian Indians: Chennai Urban Rural Epidemiology Study (CURES-67)

Objective

To estimate the prevalence of sleep abnormalities and their association with glucose intolerance and metabolic syndrome (MS) in the normal-weight urban South Indian population.

Methods

This population-based, cross-sectional study was carried out in 358 subjects aged 20–76 years randomly selected from the Chennai Urban Rural Epidemiology Study in South India. A validated questionnaire assessing various sleep abnormalities (snoring, daytime sleepiness, lack of refreshing sleep, and number of hours of sleep) was administered. All subjects underwent an oral glucose tolerance test, and anthropometric biochemical measurements were obtained to assess cardiometabolic risk factors including glucose intolerance. Diabetes risk was assessed using a previously validated Indian Diabetes Risk Score (IDRS).

Results

The overall prevalence of snoring and daytime sleepiness was 40% and 59%, respectively. Snorers were more male, older, smokers, and had higher levels of cardiometabolic risk factors. Subjects with daytime sleepiness had higher body mass index (BMI) and abdominal obesity. Both snoring (50.9% vs 30.2%, p < 0.001) and daytime sleepiness (68% vs 49.7%, p < 0.001) were more prevalent among subjects with impaired glucose metabolism compared to those with normal glucose metabolism. Both sleep measures were associated with higher diabetes risk scores, as assessed by the IDRS (snoring: trend χ², 11.14, p = 0.001; daytime sleepiness: trend χ², 5.12, p = 0.024). Metabolic syndrome was significantly associated with snoring even after adjusting for age, sex, family history of diabetes, physical activity, smoking, and alcohol.

Conclusion

The prevalence of snoring and daytime sleepiness is high among urban South Indians and these two sleep measures are associated with glucose intolerance, MS, and higher diabetes risk scores.     

No relevant relationship between glucose variability and oxidative stress in well-regulated type 2 diabetes patients

Background

A strong relationship between glycemic variability and oxidative stress in poorly regulated type 2 diabetes (T2DM) on oral medication has been reported. However, this relationship was not seen in type 1 diabetes. The purpose of this study is to reexamine the relation between glycemic variability and oxidative stress in a cohort of T2DM patients on oral medication.

Methods

Twenty-four patients with T2DM on oral glucose lowering treatment underwent 48 hours of continuous glucose monitoring (CGMS^® System Gold^TM, Medtronic MiniMed) and simultaneous collection of two consecutive 24-hour urine samples for determination of 15(S)-8-iso-prostaglandin F_2α (PGF_2α) using high-performance liquid chromatography tandem mass spectrometry. Standard deviation (SD) and mean amplitude of glycemic excursions (MAGE) were calculated as markers of glycemic variability.

Results

Included in the study were 66.7% males with a mean age (range) of 59 (36–76) years and a mean (SD) HbA1c of 6.9% (0.7). Median [interquartile range (IQR)] urinary 15(S)-8-iso-PGF_2α excretion was 176.1 (113.6–235.8) pg/mg creatinine. Median (IQR) SD was 31 (23–40) mg/dl and MAGE 85 (56–106) mg/dl. Spearman correlation did not show a significant relation for SD (ρ = 0.15, p = .49) or MAGE (ρ = 0.23, p = .29) with 15(S)-8-iso-PGF_2α excretion. Multivariate regression analysis adjusted for age, sex, HbA1c, and exercise did not alter this observation.

Conclusions

We did not find a relevant relationship between glucose variability and 15(S)-8-iso-PGF_2α excretions in T2DM patients well-regulated with oral medication that would support an interaction between hyperglycemia and glucose variability with respect to the formation of reactive oxygen species.     

The identifiable virtual patient model: comparison of simulation and clinical closed-loop study results

Background

Optimizing a closed-loop insulin delivery algorithm for individuals with type 1 diabetes can be potentially facilitated by a mathematical model of the patient. However, model simulation studies that evaluate changes to the control algorithm need to produce conclusions similar to those that would be obtained from a clinical study evaluating the same modification. We evaluated the ability of a low-order identifiable virtual patient (IVP) model to achieve this goal.

Methods

Ten adult subjects (42.5 ± 11.5 years of age; 18.0 ± 13.5 years diabetes; 6.9 ± 0.8% hemoglobin A1c) previously characterized with the IVP model were studied following the procedures independently reported in a pediatric study assessing proportional–integral–derivative control with and without a 50% meal insulin bolus. Peak postprandial glucose levels with and without the meal bolus and use of supplemental carbohydrate to treat hypoglycemia were compared using two-way analysis of variance and chi-square tests, respectively.

Results

The meal bolus decreased the peak postprandial glucose levels in both the adult-simulation and pediatric-clinical study (231 ± 38 standard deviation to 205 ± 33 mg/dl and 226 ± 51 to 194 ± 47 mg/dl, respectively; p = .0472). No differences were observed between the peak postprandial levels obtained in the two studies (clinical and simulation study not different, p = .57; interaction p = .83) or in the use of supplemental carbohydrate (3 occurrences in 17 patient days of closed-loop control in the clinical-pediatric study; 7 occurrences over 20 patient days in the adult-simulation study, p = .29).

Conclusions

Closed-loop simulations using an IVP model can predict clinical study outcomes in patients studied independently from those used to develop the model.     

Colorectal Cancer Screening in the Era of the Affordable Care Act

Background

The Affordable Care Act (ACA) eliminated cost-sharing for evidence-based preventive services in an effort to encourage use.

Objective

To evaluate use of colorectal cancer (CRC) screening in a national population-based sample before and after implementation of the ACA.

Design

Repeated cross-sectional analysis of the Medical Expenditure Panel Survey (MEPS) between 2009 and 2012 comparing CRC screening rates before and after implementation of the ACA.

Participants

Adults 50–64 with private health insurance and adults 65–75 with Medicare.

Main Measures

Self-reported receipt of screening colonoscopy, sigmoidoscopy, or fecal occult blood test (FOBT) within the past year among those eligible for screening.

Key Results

Our study included 8617 adults aged 50–64 and 3761 adults aged 65–75. MEPS response rates ranged from 58 to 63%. Among adults aged 50–64, 18.9–20.9% received a colonoscopy in the survey year, 0.59–2.1% received a sigmoidoscopy, and 7.9–10.4% received an FOBT. For adults aged 65–75, 23.6–27.7% received a colonoscopy, 1.3–3.2% a sigmoidoscopy, and 13.5–16.4% an FOBT. In adjusted analyses, among participants aged 50–64, there was no increase in yearly rates of colonoscopy (−0.28 percentage points, 95% CI −2.3 to 1.7, p = 0.78), sigmoidoscopy (−1.1%, 95% CI −1.7 to −0.46, p = <0.001), or FOBT (−1.6%, 95% CI −3.2 to −0.03, p = 0.046) post-ACA. For those aged 65–75, rates of colonoscopy (+2.3%, 95% CI −1.4 to 6.0, p = 0.22), sigmoidoscopy (+0.34%, 95% CI 0.88 to 1.6, p = 0.58) and FOBT (−0.65, 95% CI −4.1 to 2.8, p = 0.72) did not increase. Among those aged 65–75 with Medicare and no additional insurance, the use of colonoscopy rose by 12.0% (95% CI 3.3 to 20.8, p = 0.007). Among participants with Medicare living in poverty, colonoscopy use also increased (+5.7%, 95% CI 0.18 to 11.3, p = 0.043).

Conclusions

Eliminating cost-sharing for CRC screening has not resulted in changes in the use of CRC screening services for many Americans, although use may have increased in the post-ACA period among some Medicare beneficiaries.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-015-3504-2) contains supplementary material, which is available to authorized users.KEY WORDS: colorectal cancer, health care reform, health insurance, preventive care     

Effect of diabetes mellitus on outcomes of hyperglycemia in a mixed medical surgical intensive care unit

Background:

Intensive insulin therapy and degree of glycemic control in critically ill patients remains controversial, particularly in patients with diabetes mellitus. We hypothesized that diabetic patients who achieved tight glucose control with continuous insulin therapy would have less morbidity and lower mortality than diabetic patients with uncontrolled blood glucose.

Method:

A retrospective chart review was performed on 395 intensive care unit (ICU) patients that included 235 diabetic patients. All patients received an intravenous insulin protocol targeted to a blood glucose (BG) level of 80–140mg/dl. Outcomes were compared between (a) nondiabetic and diabetic patients, (b) diabetic patients with controlled BG levels (80–140mg/dl) versus uncontrolled levels (>140 mg/dl), and (c) diabetic survivors and nonsurvivors.

Results:

Diabetic patients had a shorter ICU stay compared to nondiabetic patients (10 ± 0.7 vs 13 ± 1.1, p = .01). The mean BG of the diabetic patients was 25% higher on average in the uncontrolled group than in the controlled (166 ± 26 vs 130 ± 9.4 mg/dl, p < .01). There was no difference in ICU and hospital length of stay (LOS) between diabetic patients who were well controlled compared to those who were uncontrolled. Diabetic nonsurvivors had a significantly higher incidence of hypoglycemia (BG <60 mg/dl) compared to diabetic survivors.

Conclusion:

The results showed that a diagnosis of diabetes was not an independent predictor of mortality, and that diabetic patients who were uncontrolled did not have worse outcomes. Diabetic nonsurvivors were associated with a greater amount of hypoglycemic episodes, suggesting these patients may benefit from a more lenient blood glucose protocol.     

Effects of a structured self-monitoring of blood glucose method on patient self-management behavior and metabolic outcomes in type 2 diabetes mellitus

Background

The purpose of this study was to evaluate the effect of structured self-monitoring of blood glucose (SMBG) on patient self-management behavior and metabolic outcomes in patients with type 2 diabetes mellitus (T2DM).

Methods

From January to June 2009, 30 patients with basic diabetes education were followed for a period of 90 days. To provide assessment of glycemic control and frequency of dysglycemia, patients, underwent 3 consecutive days of seven-point SMBG during each month for 3 consecutive months, using the ACCU-CHEK 360° View tool. Glucose profiles of the first and third month were used for comparison.

Results

Hemoglobin A1c (HbA1c) improved significantly during the 90-day period in all patients [confidence interval (CI) 95%, 0.32–1.64%, p < .05] and those with poor metabolic control (group B; CI 95%, 0.86–2.64%, p < .05). Mean blood glucose (MBG) values decreased significantly in group B (CI 95%, 0.56–24.78 mg/dl, p < .05) and all cases (CI 95%, 1.61–19.73 mg/dl, p < .05). Meanwhile, there was an average decrease of 15.7 mg/dl in fasting blood sugar (FBS) levels in the whole subjects. Mean postprandial blood glucose levels (MPP) decreased by 19.3 and 11.3 mg/dl in group B and in all cases, respectively. However, there were no significant changes in HbA1c, MBG, FBS, and MPP in people with good metabolic control.

Conclusion

A structured SMBG program improves HbA1c, FBS, MPP, and MBG in people with poorly controlled diabetes. This improvement shows the importance of patient self-management behavior on metabolic outcomes in T2DM.     

Retinal vascular geometry in Asian persons with diabetes and retinopathy

Purpose

Our purpose was to examine the relationship of retinal vascular parameters with diabetes and retinopathy in an older Asian population.

Methods

Retinal photographs from participants of a population-based survey of Asian Malay persons aged 40–80 years were analyzed. Specific retinal vascular parameters (tortuosity, branching angle, fractal dimension, and caliber) were measured using a semiautomated computer-based program. Diabetes was defined as random plasma glucose ≥ 11.1 mmol/liter, the use of diabetes medication, or physician-diagnosed diabetes. Retinopathy signs were graded from photographs using the modified Airlie House classification system.

Results

A total of 2735 persons were included in the study. Persons with diabetes (n = 594) were more likely to have straighter (less tortuous) arterioles and wider arteriolar and venular caliber than those without diabetes (n = 2141). Among subjects with diabetes, those with retinopathy had wider venular caliber than those without retinopathy (211.3 versus 204.9 mm, p = .001). Among nondiabetic subjects, however, those with retinopathy had more tortuous venules than those without retinopathy [5.19(×10⁴) versus 4.27(×10⁴), p < .001].

Conclusions

Retinal vascular parameters varied by diabetes and retinopathy status in this older Asian cohort. Our findings suggest that subtle alterations in retinal vascular architecture are influenced by diabetes.     

The effect of real-time continuous glucose monitoring on glycemic control in patients with type 2 diabetes mellitus

Background:

Real-time continuous glucose monitoring (RT-CGM) improves hemoglobin A1c (A1C) and hypoglycemia in people with type 1 diabetes mellitus and those with type 2 diabetes mellitus (T2DM) on prandial insulin; however, it has not been tested in people with T2DM not taking prandial insulin. We evaluated the utility of RT-CGM in people with T2DM on a variety of treatment modalities except prandial insulin.

Methods:

We conducted a prospective, 52-week, two-arm, randomized trial comparing RT-CGM (n = 50) versus self-monitoring of blood glucose (SMBG) (n = 50) in people with T2DM not taking prandial insulin. Real-time continuous glucose monitoring was used for four 2-week cycles (2 weeks on/1 week off). All patients were managed by their usual provider. This article reports on changes in A1C 0–12 weeks.

Results:

Mean (±standard deviation) decline in A1C at 12 weeks was 1.0% (±1.1%) in the RT-CGM group and 0.5% (±0.8%) in the SMBG group (p = .006). There were no group differences in the net change in number or dosage of hypoglycemic medications. Those who used the RT-CGM for ≥48 days (per protocol) reduced their A1C by 1.2% (±1.1%) versus 0.6% (±1.1%) in those who used it <48 days (p = .003). Multiple regression analyses statistically adjusting for baseline A1C, an indicator for usage, and known confounders confirmed the observed differences between treatment groups were robust (p = .009). There was no improvement in weight or blood pressure.

Conclusions:

Real-time continuous glucose monitoring significantly improves A1C compared with SMBG in patients with T2DM not taking prandial insulin. This technology might benefit a wider population of people with diabetes than previously thought.     

Impact of Different Fat Depots on Insulin Sensitivity: Predominant Role of Liver Fat

Background

Overall obesity and, as it is increasingly appreciated, body fat distribution and ectopic fat deposition in liver and skeletal muscle, determine insulin resistance in humans. However, little is known about the independence of these relationships. Therefore, we determined the impact of different fat depots as well as fat accumulation in ectopic tissues such as liver and skeletal muscle in the prediction of insulin resistance in healthy humans.

Methods

Visceral and subcutaneous abdominal fat were determined by magnetic resonance (MR) tomography and liver fat and intramyocellular fat in the tibialis anterior muscle by ¹H-MR spectroscopy in 220 subjects. Insulin sensitivity was estimated from the oral glucose tolerance test (OGTT) and measured by a euglycemic hyperinsulinemic clamp in a subgroup (n = 157).

Results

Insulin sensitivity estimated from the OGTT correlated negatively with total body fat (r = −0.27, p < 0.0001), subcutaneous abdominal fat (r = −0.35, p < 0.0001), and visceral fat (r = −0.43, p < 0.0001). Furthermore, insulin sensitivity correlated negatively with liver fat (r = −0.53, p < 0.0001) and intramyocellular fat (r = −0.26, p < 0.0001). In multivariate regression models, high liver and visceral fat emerged as the strongest predictors of low insulin sensitivity.

Conclusion

Among various fat compartments, high liver fat and high visceral fat are the strongest determinants of insulin sensitivity in humans.     

A Single-Center, Open, Comparative Study of the Effect of Using Self-Monitoring of Blood Glucose to Guide Therapy on Preclinical Atherosclerotic Markers in Type 2 Diabetic Subjects

Background

The aim of our study was to determine the effect of treatment based on preprandial and postprandial self-monitoring of blood glucose (SMBG) on the progression of carotid intima-medial thickness (CIMT) in noninsulin-treated type 2 diabetes mellitus (T2DM) subjects.

Methods

In this 18-month prospective trial, we recruited subjects 18–70 years of age, treated with metformin and sulfonylurea, with a standardized hemoglobin A1c (HbA1c) level ≤9.0%. Subjects were randomized to use of fasting/preprandial (FP) SMBG results to adjust evening medication or use of postprandial (PP) SMBG results to adjust morning medication. The primary end point was change in CIMT; change in HbA1c was a secondary end point.

Results

Of the 300 subjects randomized, 280 (140 in each group) completed all biochemical tests and CIMT analysis. Carotid intima-medial thickness was reduced significantly in PP subjects from 0.78 (±0.15) mm to 0.73 (±0.14) mm (p < 0.005), but no significant CIMT reduction was seen in FP subjects. A significant reduction in HbA1c was also seen in the PP group (p < 0.005) but not in the FP group 1 (p = 0.165). Significant improvements in body mass index (p = 0.038), waist circumference (p < 0.001), systolic blood pressure (p = 0.008), and serum cholesterol (p = 0.02) were also seen in PP subjects but not in FP subjects.

Conclusion

Use of postprandial SMBG data to adjust therapy was associated with a significant regression of carotid intima-medial thickening and a reduction in HbA1c in T2DM, whereas no significant improvement in these parameters was seen in subjects who used fasting/preprandial SMBG data for therapy adjustment.     

FreeStyle Mini? Blood Glucose Results Are Accurate and Suitable for Use in Glycemic Clamp Protocols

Objective

We assessed the accuracy of the FreeStyle Mini™ (FSM) meter for use in glycemic clamp and meal protocols in comparison with the HemoCue Glucose 201 DM Analyzer (HemoCue) and the YSI 2300 STAT Glucose Oxidase Analyzer (YSI).

Methods

Seven volunteers with type 2 diabetes mellitus, 35–69 years old, underwent a frequently sampled meal test and a graded hyperglycemic test, on two separate days, with one of the volunteers undergoing each test twice. Samples for glucose measurements were obtained from arterialized venous blood. A total of 420 samples (with glucose levels ranging from 63 to 388 mg/dl) were available for comparison. On average, 10 measurements were available for every 5 mg/dl increment in glucose level in the range of 130–310 mg/dl. Blood glucose measurements were done on each sample with the FSM, HemoCue, and YSI.

Results

FreeStyle Mini blood glucose values correlated closely with the YSI readings. Of the FSM measurements, 99.0% were within the Clarke error grid zone A; 51.3%, 84.7%, and 96.2% of the FSM readings were within 5%, 10% and 15% of the YSI values, respectively. The FSM was significantly more accurate than the HemoCue (84.7% vs 76.6% of results within 10% of the YSI results; p = .0038). The mean average relative difference of the FSM (5.8%) was also significantly lower than that of the HemoCue (6.8%; p = .0013)

Conclusions

The FSM provides accurate results and constitutes a suitable alternative for bedside blood glucose measurements in experimental procedures, helping to reduce sample size, turnaround time, and cost.     

Concealed Maternal Blood Glucose Excursions Correlate with Birth Weight Centile

Background

The objective of this study was to test the hypothesis that maternal blood glucose excursions correlate with deviation from optimized birth weight.

Methods

Patients were recruited for 3-day continuous glucose monitoring (CGM) plus self-blood glucose monitoring followed by routine diabetes screening at 26-28 weeks gestation. Patients and caregivers were blinded to CGM results. The magnitude and duration of blood glucose (BG) excursions were measured as a “glycemia index.” A customized birth weight centile was calculated.

Results

Twenty-three patients consented, 21 completed the study: 5 diabetic and 16 nondiabetic individuals. The duration of CGM was 72 (±7.2) hours, and each patient performed self-BG monitoring ≥3 times per day. All diabetic and 10 nondiabetic patients had several measured BG excursions above 130 mg/dl. A positive correlation was observed between birth weight centile and glycemia index above 130 (p < 0.03); the trend persisted for nondiabetic patients alone (p < 0.05). No significant correlation was noted between birth weight centile and average 3-day CGM values, 3-day fasting BG, average 3-day self-BG monitoring values, or diabetes screening BG value.

Conclusions

The glycemia index has a better correlation with birth weight centile than BG measured by conventional methods in a mixed diabetic and nondiabetic population. Fetal exposure to maternal blood glucose excursions correlates positively with fetal growth, even in nondiabetic patients with apparently normal glucose tolerance.     

Correlation between plantar foot temperature and diabetic neuropathy: a case study by using an infrared thermal imaging technique

Background

Diabetic neuropathy consists of multiple clinical manifestations of which loss of sensation is most prominent. High temperatures under the foot coupled with reduced or complete loss of sensation can predispose the patient to foot ulceration. The aim of this study was to look at the correlation between plantar foot temperature and diabetic neuropathy using a noninvasive infrared thermal imaging technique.

Methods

Infrared thermal imaging, a remote and noncontact experimental tool, was used to study the plantar foot temperatures of 112 subjects with type 2 diabetes selected from a tertiary diabetes centre in South India.

Results

Patients with diabetic neuropathy (defined as vibration perception threshold (VPT) values on biothesiometry greater than 20 V) had a higher foot temperature (32–35 °C) compared to patients without neuropathy (27–30 °C). Diabetic subjects with neuropathy also had higher mean foot temperature (MFT) (p = .001) compared to non-neuropathic subjects. MFT also showed a positive correlation with right great toe (r = 0.301, p = .001) and left great toe VPT values (r = 0.292, p = .002). However, there was no correlation between glycated hemoglobin and MFT.

Conclusion

Infrared thermal imaging may be used as an additional tool for evaluation of high risk diabetic feet.