Lipohypertrophy Monitoring Study (LIMO): Effect of single use of 4 mm pen needles combined with education on injection site rotation on glycaemic control: Confirmation of an unpleasant truth.

AIMS: To investigate whether single use of 4 mm needles combined with education about injection technique and lipohypertrophy affects HbA1c, hypoglycaemia and glucose variability. METHODS: Insulin-injecting people with diabetes recruited from nine Belgian diabetes centres were prospectively followed for 6 months. They were provided 4 mm pen needles and education concerning injection technique using an online platform (BD and Me™) based on the international Forum for Injection Technique & Therapy Recommendations focused on avoidance of lipohypertrophy zones and reduction of needle reuse. RESULTS: A total of 171 people with diabetes were included of which 146 completed the study. At baseline, lipohypertrophy was present in 63.0% of those who completed the study, with 51.4% injecting in zones of lipohypertrophy, 37.0% incorrectly rotating and 95.9% reusing needles. After the intervention, 7.5% still injected in a lipohypertrophy zone, 4.1% rotated incorrectly and needle reuse decreased to 21.2%. The number of participants with severe hypoglycaemias (from 15.8% to 4.1%, p < 0.001), unexplained hypoglycaemias (from 46.6% to 16.4%, p < 0.001) and high glucose variability (from 64.4% to 29.5%, p < 0.001) was significantly reduced. HbA1c and total daily insulin dose remained stable. CONCLUSION: The combination of 4 mm pen needles and online education on injection techniques significantly reduced the number of people with severe hypoglycaemic episodes, unexplained hypoglycaemia and high glucose variability but did not improve HbA1c control nor lower insulin needs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04659330.

THE ADDED AND INTERPRETATIVE VALUE OF CGM-DERIVED PARAMETERS IN TYPE 1 DIABETES DEPENDS ON THE LEVEL OF GLYCEMIC CONTROL.

OBJECTIVE: In type 1 diabetes mellitus (T1DM) management, continuous glucose monitoring (CGM)-derived parameters can provide additional insights, with time in range (TIR) and other parameters reflecting glycemic control and variability being put forward. This study aimed to examine the added and interpretative value of the CGM-derived indices TIR and coefficient of variation (CV%) in T1DM patients stratified according to their level of glycemic control by means of HbA1C. METHODS: T1DM patients with a minimum disease duration of 10 years and without known macrovascular disease were enrolled. Patients were equipped with a blinded CGM device for 7 days. TIR and time spent in hypoglycemia and hyperglycemia were determined, and CV% was used as a parameter for glycemic variability. Pearson (r) and Spearman correlations (rs) and a regression analysis were used to examine associations. RESULTS: Ninety-five patients (age: 45 ± 10 years; HbA1C level: 7.7% ± 0.8% [61 ± 7 mmol/mol]) were included (mean blood glucose [MBG]: 159 ± 31 mg/dL; TIR: 55.8% ± 14.9%; CV%: 43.5% ± 7.8%) and labeled as having good (HbA1C level ≤7% [≤53 mmol/mol]; n = 20), moderate (7%-8%; n = 44), or poor (>8% [>64 mmol/mol]; n = 31) glycemic control. HbA1C was significantly associated with MBG (rs = 0.48, P < .001) and time spent in hyperglycemia (total: rs = 0.52; level 2: r = 0.46; P < .001) but not with time spent in hypoglycemia and CV%, even after an analysis of the HbA1C subgroups. Similarly, TIR was negatively associated with HbA1C (r = -0.53; P < .001), MBG (rs = -0.81; P < .001), and time spent in hyperglycemia (total: rs = -0.90; level 2: rs = -0.84; P < .001) but not with time in hypoglycemia. The subgroup analyses, however, showed that TIR was associated with shorter time spent in level-2 hypoglycemia in patients with good (rs = -0.60; P = .007) and moderate (rs = -0.25; P = .047) glycemic control. In contrast, CV% was strongly positively associated with time in hypoglycemia (total: rs = 0.78; level 2: rs = 0.76; P < .001) but not with TIR or time in hyperglycemia in the entire cohort, although the subgroup analyses showed that TIR was negatively associated with CV% in patients with good glycemic control (r = -0.81, P < .001) and positively associated in patients with poor glycemic control (r = +0.47; P < .01). CONCLUSION: The CGM-derived metrics TIR and CV% are related to clinically important situations, TIR being strongly dependent on hyperglycemia and CV% being reflective of hypoglycemic risk. However, the interpretation and applicability of TIR and CV% and their relationship depends on the level of glycemic control of the individual patient, with CV% generally adding less clinically relevant information in those with poor control. This illustrates the need for further research and evaluation of composite measures of glycemic control in T1DM.

The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes: A systematic review.

Rigorous glycaemic control-reflected by low HbA1c goals-is of the utmost importance in the prevention and management of complications in patients with type 1 diabetes mellitus (T1DM). However, previous studies suggested that short-term glycaemic variability (GV) is also important to consider as excessive glucose fluctuations may have an additional impact on the development of diabetic complications. The potential relationship between GV and the risk of cardiovascular autonomic neuropathy (CAN), a clinical expression of cardiovascular autonomic dysfunction, is of increasing interest. This systematic review aimed to summarize existing evidence concerning the relationship between GV and cardiovascular autonomic dysfunction in T1DM. An electronic database search of Medline (PubMed), Web of Science and Embase was performed up to October 2019. There were no limits concerning year of publication. Methodological quality was evaluated using the Newcastle Ottawa Scale for observational studies. Six studies (four cross-sectional and two prospective cohorts) were included. Methodological quality of the studies varied from level C to A2. Two studies examined the association between GV and heart rate variability (HRV), and both found significant negative correlations. Regarding cardiovascular autonomic reflex tests (CARTs), two studies did not, while two other studies did find significant associations between GV parameters and CART scores. However, associations were attenuated after adjusting for covariates such as HbA1c, age and disease duration. In conclusion, this systematic review found some preliminary evidence supporting an association between GV and cardiovascular autonomic dysfunction in T1DM. Hence, uncertainty remains whether high GV can independently contribute to the onset or progression of CAN. The heterogeneity in the methodological approach made it difficult to compare different studies. Future studies should therefore use uniformly evaluated continuous glucose monitoring-derived parameters of GV, while standardized assessment of HRV, CARTs and other potential cardiac autonomic function parameters is needed for an unambiguous definition of CAN.

Two-stage, school and community-based population screening successfully identifies individuals and families at high-risk for type 2 diabetes: the Feel4Diabetes-study.

BACKGROUND: The implementation of population screening and early prevention strategies targeting individuals at high-risk for type 2 diabetes (T2D) seems to be a public health priority. The current work aimed to describe the screening procedure applied in the Feel4Diabetes-study and examine its effectiveness in identifying individuals and families at high risk, primarily for T2D and secondarily for hypertension, among vulnerable populations in low to middle-income countries (LMICs) and high-income countries (HICs) across Europe. METHODS: A two-stage screening procedure, using primary schools as the entry-point to the community, was applied in low socioeconomic status (SES) regions in LMICs (Bulgaria-Hungary), HICs (Belgium-Finland) and HICs under austerity measures (Greece-Spain). During the first-stage screening via the school-setting, a total of 20,501 parents (mothers and/or fathers) of schoolchildren from 11,396 families completed the Finnish Diabetes Risk Score (FINDRISC) questionnaire, while their children underwent anthropometric measurements in the school setting. Parents from the identified "high-risk families" (n = 4484) were invited to participate in the second-stage screening, including the measurement of fasting plasma glucose (FPG) and blood pressure (BP). In total, 3153 parents participated in the second-stage screening (mean age 41.1 ± 5.6 years, 65.8% females). RESULTS: Among parents who attended the second-stage screening, the prevalence of prediabetes (as defined by impaired fasting glucose; FPG 100-125 mg/dl) and T2D (FPG > 126 mg/dl) was 23.2 and 3.0% respectively, and it was found to be higher in the higher FINDRISC categories. The percentage of undiagnosed T2D among the participants identified with T2D was 53.5%. The prevalence of high normal BP (systolic BP 130-139 mmHg and/ or diastolic BP 85-89 mmHg) and hypertension (systolic BP ≥ 140 mmHg and/ or diastolic BP ≥ 90 mmHg) was 14 and 18.6% respectively, which was also higher in the higher FINDRISC categories. The percentage of cases not receiving antihypertensive treatment among the participants identified with hypertension was 80.3%. CONCLUSION: The findings of the current study indicate that the two-stage school and community-based screening procedure followed, effectively identified high-risk individuals and families in vulnerable populations across Europe. This approach could be potentially scalable and sustainable and support initiatives for the early prevention of T2D and hypertension. TRIAL REGISTRATION: The Feel4Diabetes-intervention is registered at https://clinicaltrials.gov/ (NCT02393872; date of trial registration: March 20, 2015).

Effectiveness of a family-, school- and community-based intervention on physical activity and its correlates in Belgian families with an increased risk for type 2 diabetes mellitus: the Feel4Diabetes-study.

BACKGROUND: The study aimed to investigate the effectiveness of the European Feel4Diabetes intervention, promoting a healthy lifestyle, on physical activity and its correlates among families at risk for type 2 diabetes mellitus (based on the Finnish Diabetes Risk Score) in Belgium. METHODS: The Feel4Diabetes intervention involved three components: family, school and community component, with the family component consisting of 6 counseling sessions for families at risk. Main outcomes were objectively measured physical activity levels and its subjectively measured correlates. The final sample consisted of 454 parents (mean age 39.4 years; 72.0% women) and 444 children (mean age 8.0 years; 50.1% girls). Multilevel repeated measures analyses were performed to assess intervention effectiveness after 1 year. RESULTS: In parents, there was no significant intervention effect. In children, there were only significant negative effects for moderate to vigorous physical activity (p = 0.05; ηp2 = 0.008) and steps (p = 0.03; ηp2 = 0.006%) on weekdays, with physical activity decreasing (more) in the intervention group. CONCLUSIONS: The F4D-intervention lacks effectiveness on high-risk families' physical activity and its correlates in Belgium. This could partially be explained by low attendance rates and a large drop-out. To reach vulnerable populations, future interventions should invest in more appropriate recruitment (e.g. more face-to-face contact) and more bottom-up development of the intervention (i.e. co-creation of the intervention with the target group). TRIAL REGISTRATION: The Feel4Diabetes-study was prospectively registered at clinicaltrials.gov as NCT02393872 on 20 March 2015.

Efficacy of a Self-Regulation-Based Electronic and Mobile Health Intervention Targeting an Active Lifestyle in Adults Having Type 2 Diabetes and in Adults Aged 50 Years or Older: Two Randomized Controlled Trials.

BACKGROUND: Adopting an active lifestyle plays a key role in the prevention and management of chronic diseases such as type 2 diabetes mellitus (T2DM). Web-based interventions are able to alter health behaviors and show stronger effects when they are informed by a behavior change theory. MyPlan 2.0 is a fully automated electronic health (eHealth) and mobile health (mHealth) intervention targeting physical activity (PA) and sedentary behavior (SB) based on the Health Action Process Approach (HAPA). OBJECTIVE: This study aimed to test the short-term effect of MyPlan 2.0 in altering levels of PA and SB and in changing personal determinants of behavior in adults with T2DM and in adults aged ≥50 years. METHODS: The study comprised two randomized controlled trials (RCTs) with an identical design. RCT 1 was conducted with adults with T2DM. RCT 2 was performed in adults aged ≥50 years. Data were collected via face-to-face assessments. The participants decided either to increase their level of PA or to decrease their level of SB. The participants were randomly allocated with a 2:1 ratio to the intervention group or the waiting-list control group. They were not blinded for their group allocation. The participants in the intervention group were instructed to go through MyPlan 2.0, comprising 5 sessions with an interval of 1 week between each session. The primary outcomes were objectively measured and self-reported PA (ie, light PA, moderate-to-vigorous PA, total PA, number of steps, and domain-specific [eg, transport-related] PA) and SB (ie, sitting time, number of breaks from sitting time, and length of sitting bouts). Secondary outcomes were self-reported behavioral determinants for PA and SB (eg, self-efficacy). Separate linear mixed models were performed to analyze the effects of MyPlan 2.0 in the two samples. RESULTS: In RCT 1 (n=54), the PA intervention group showed, in contrast to the control group, a decrease in self-reported time spent sitting (P=.09) and an increase in accelerometer-measured moderate (P=.05) and moderate-to-vigorous PA (P=.049). The SB intervention group displayed an increase in accelerometer-assessed breaks from sedentary time in comparison with the control group (P=.005). A total of 14 participants of RCT 1 dropped out. In RCT 2 (n=63), the PA intervention group showed an increase for self-reported total PA in comparison with the control group (P=.003). Furthermore, in contrast to the control group, the SB intervention group decreased their self-reported time spent sitting (P=.08) and increased their accelerometer-assessed moderate (P=.06) and moderate-to-vigorous PA (P=.07). A total of 8 participants of RCT 2 dropped out. CONCLUSIONS: For both the samples, the HAPA-based eHealth and mHealth intervention, MyPlan 2.0, was able to improve only some of the primary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03291171; http://clinicaltrials.gov/ct2/show/NCT03291171. ClinicalTrials.gov NCT03799146; http://clinicaltrials.gov/ct2/show/NCT03799146. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/12413.

Analysis of protein glycation in human fingernail clippings with near-infrared (NIR) spectroscopy as an alternative technique for the diagnosis of diabetes mellitus.

BACKGROUND: Glycated keratin allows the monitoring of average tissue glucose exposure over previous weeks. In the present study, we wanted to explore if near-infrared (NIR) spectroscopy could be used as a non-invasive diagnostic tool for assessing glycation in diabetes mellitus. METHODS: A total of 52 patients with diabetes mellitus and 107 healthy subjects were enrolled in this study. A limited number (n=21) of nails of healthy subjects were glycated in vitro with 0.278 mol/L, 0.556 mol/L and 0.833 mol/L glucose solution to study the effect of glucose on the nail spectrum. Consequently, the nail clippings of the patients were analyzed using a Thermo Fisher Antaris II Near-IR Analyzer Spectrometer and near infrared (NIR) chemical imaging. Spectral classification (patients with diabetes mellitus vs. healthy subjects) was performed using partial least square discriminant analysis (PLS-DA). RESULTS: In vitro glycation resulted in peak sharpening between 4300 and 4400 cm-1 and spectral variations at 5270 cm-1 and between 6600 and 7500 cm-1. Similar regions encountered spectral deviations during analysis of the patients' nails. Optimization of the spectral collection parameters was necessary in order to distinguish a large dataset. Spectra had to be collected at 16 cm-1, 128 scans, region 4000-7500 cm-1. Using standard normal variate, Savitsky-Golay smoothing (7 points) and first derivative preprocessing allowed for the prediction of the test set with 100% correct assignments utilizing a PLS-DA model. CONCLUSIONS: Analysis of protein glycation in human fingernail clippings with NIR spectroscopy could be an alternative affordable technique for the diagnosis of diabetes mellitus.

LONG-TERM, SUSTAINED, LIFESTYLE-INDUCED WEIGHT LOSS IN SEVERE OBESITY: THE GET-ReAL PROGRAM.

OBJECTIVE: To study the long-term effectiveness of a patient-centered, multidisciplinary lifestyle intervention treatment in patients medically eligible for bariatric surgery. METHODS: Using a case-control study design, we compared treatment results for 98 adults (mean body mass index [BMI], 44.2 kg/m(2)) with the outcomes of 148 controls (mean BMI, 43.0 kg/m(2)) receiving standard care. The approach included a phased triage for inclusion, followed by 12 lifestyle intervention group sessions alternating with individual visits for behavior, diet, and exercise instructions. RESULTS: At 2 years, weight loss averaged 15.3 ± 1.4 kg (P<.0010) (12 ± 1% of initial body weight [IBW], P<.001; 21 ± 2% of excess body weight [EBW], P<.001) in an intention-to-treat (ITT) analysis; in completers, weight loss was 18.8 ± 1.5 kg (P<.001) (15 ± 1% IBW, P<.001; 26 ± 3% EBW, P<.001). A total of 42 patients lost ≥10% IBW. Controls remained weight stable (P = .35); 3% lost ≥10% IBW. Patients achieving weight loss that would be considered satisfactory for bariatric surgery included 20% who achieved ≥35% EBW loss, 29% who achieved a BMI <35 kg/m(2) (if starting BMI <50 kg/m(2)) or BMI <40 kg/m(2) (if starting BMI ≥50 kg/m(2)), and 37% who achieved EBW loss ≤50%. These values for completers were 31, 39, and 48%, respectively. In the 55 patients starting the program ≥4 years ago, weight loss maintenance of 12 ± 1% IBW (ITT, 16 ± 1% in completers) was observed. CONCLUSION: Substantial nonsurgical weight loss, maintained at 2 to 4 years, is achievable in severely obese patients using comprehensive lifestyle approaches; the efficacy/safety trade-off in obesity treatment is an important consideration in interpreting these results.

Hyperinsulinemia and skeletal muscle fatty acid trafficking.

We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-¹³C]palmitate (0400-0900 h) and [U-¹³C]oleate (0800-1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass⁻¹·min⁻¹) clamp (0800-1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-¹³C]palmitate incorporation into imTG-palmitate and palmitoylcarnitine were similar to those we reported in overnight postabsorptive adults (saline control); the intramyocellular palmitoylcarnitine enrichment was not different from and correlated with imTG-palmitate enrichment for both the morning (r = 0.38, P = 0.02) and afternoon (r = 0.44, P = 0.006) biopsy samples. Plasma FFA concentrations, flux, and the incorporation of plasma oleate into imTG-oleate during hyperinsulinemia were ~1/10th of that observed in the previous saline control studies (P < 0.001). At the time of the second biopsy, the enrichment in oleoylcarnitine was <25% of that in imTG-oleate and was not correlated with imTG-oleate enrichment. The intramyocellular nonesterified fatty acid-palmitate-to-imTG-palmitate enrichment ratio was greater (P < 0.05) in women than men, suggesting that sex differences in intramyocellular palmitate trafficking may occur under hyperinsulinemic conditions. We conclude that plasma FFA trafficking into imTG during hyperinsulinemia is markedly suppressed, and these newly incorporated FFA fatty acids do not readily enter the LCAC preoxidative pools. Hyperinsulinemia does not seem to inhibit the entry of fatty acids from imTG pools that were labeled under fasting conditions, possibly reflecting the presence of two distinct imTG pools that are differentially regulated by insulin.

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a high risk of vascular complications. Interestingly, cocoa flavanols (CF) can exert beneficial vascular effects in non-diabetic subjects. However, these effects have only been scarcely studied in T2DM. Therefore, we performed a study to assess the effects on vascular reactivity of a single dose of CF (790 mg) in T2DM and whether certain antihypertensive drugs may modulate these effects. METHODS: 24 non-diabetic and 11 T2DM subjects were studied in a cross-over design. Fasting blood samples, blood pressure (BP), and arterial vasoreactivity (flow-mediated dilation) were assessed before and 70 min after capsule ingestion. Muscle microvascular reactivity was only assessed after capsule ingestion. Age, waist-to-hip ratio, BP at baseline, and the use of antihypertensive drugs were regarded as covariates in a mixed models analysis. RESULTS: CF ingestion did not affect any parameter. However, independent of the type of capsules ingested, a decrease in diastolic BP by 3 mmHg (95% CI: -4.0; -2.0) and an increase in the change in brachial artery diameter (pre vs. post occlusion) by 0.06 mm (95% CI: 0.01; 0.12) were detected in the non-diabetic group, while they remained unchanged in the T2DM group. CONCLUSION: No beneficial effects of CF were detected on vascular reactivity parameters in T2DM and non-diabetic participants.

Simvastatin-induced erythromelalgia: less is more.

We describe a case of a woman with uncomplicated Type 2 diabetes mellitus, presenting with severe burning pains and intense redness of the legs, for which only cooling could provide relief. Although the description was classic of erythromelalgia, the lack of familiarity of the disorder caused considerable doctor's delay as well as the erroneous advice to start pain killers and amitriptyline. However, empirical discontinuation of simvastatin made all symptoms disappear. Erthyromelalgia is a rare but debilitating disease which is diagnosed by exclusion only. It usually occurs as a secondary feature to (hematologic) malignant disorders, autoimmune diseases or, infections or, most notoriously, to pharmacological agents. One of the latter might be simvastatin, and possibly all HMG CoA Reductase inhibitors.

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension: A Protocol for an Acute, Randomized, Double-Blinded, Placebo-Controlled Cross-Over Trial.

Introduction: Patients with type 2 diabetes mellitus are at high risk to develop vascular complications resulting in high morbidity and mortality. Cocoa flavanols are promising nutraceuticals with possible beneficial vascular effects in humans. However, limited research is currently available on the vascular effects in a diabetic population with inconsistent results. Possible reasons for this inconsistency might be heterogeneity in the given intervention (dose per time and day, single dose vs. split-dose, placebo formula) and the studied population (blood pressure at baseline, duration of diabetes, use of vasoactive antihypertensive and antidiabetic drugs, sex). Therefore, we aimed to develop a randomized, double-blinded, placebo-controlled cross-over trial to investigate whether cocoa flavanols have an acute impact on blood pressure and vascular reactivity in patients with type 2 diabetes with and without arterial hypertension. Methods and Analysis: We will include participants in four groups: (i) patients with type 2 diabetes without arterial hypertension, (ii) patients with type 2 diabetes with arterial hypertension and 1 antihypertensive drug, (iii) non-diabetic participants with essential hypertension and 1 antihypertensive drug, and (iv) healthy controls. All participants will complete the same protocol on both testing days, consuming high-flavanol cocoa extract (790 mg flavanols) or placebo. Macrovascular endothelial function (flow-mediated dilation) and blood pressure will be measured before and after capsule ingestion. Forearm muscle vasoreactivity (near-infrared spectroscopy) and brachial artery blood flow (echo-doppler) will be assessed in response to a dynamic handgrip exercise test after capsule ingestion. Data will be analyzed with a random intercept model in mixed models. Clinical Trial Registration: www.Clinicaltrials.gov, identifier: NCT03722199.

Development and Validation of Two Self-Reported Tools for Insulin Resistance and Hypertension Risk Assessment in A European Cohort: The Feel4Diabetes-Study.

Early identification of type 2 diabetes mellitus (T2DM) and hypertension (HTN) risk may improve prevention and promote public health. Implementation of self-reported scores for risk assessment provides an alternative cost-effective tool. The study aimed to develop and validate two easy-to-apply screening tools identifying high-risk individuals for insulin resistance (IR) and HTN in a European cohort. Sociodemographic, lifestyle, anthropometric and clinical data obtained from 1581 and 1350 adults (baseline data from the Feel4Diabetes-study) were used for the European IR and the European HTN risk assessment index respectively. Body mass index, waist circumference, sex, age, breakfast consumption, alcohol, legumes and sugary drinks intake, physical activity and sedentary behavior were significantly correlated with Homeostatic Model Assessment of IR (HOMA-IR) and/or HTN and incorporated in the two models. For the IR index, the Area Under the Curve (AUC), sensitivity and specificity for identifying individuals above the 75th and 95th of HOMA-IR percentiles were 0.768 (95%CI: 0.721-0.815), 0.720 and 0.691 and 0.828 (95%CI: 0.766-0.890), 0.696 and 0.778 respectively. For the HTN index, the AUC, sensitivity and specificity were 0.778 (95%CI: 0.680-0.876), 0.667 and 0.797. The developed risk assessment tools are easy-to-apply, valid, and low-cost, identifying European adults at high risk for developing T2DM or having HTN.

Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People.

OBJECTIVE: The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study. RESEARCH DESIGN AND METHODS: Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated. RESULTS: In TM, body weight (2.8 ± 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P < 0.01), and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01) increased. Fasting insulin (-1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (-1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (-1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (-0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] × min; P < 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] × min; P < 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg; P = 0.07) with decreasing FFM (-2.3 ± 0.4 kg; P < 0.01) and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01). Insulin (3.4 ± 0.8 mU/L; P < 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P < 0.01) rose, fasting GIP (-1.4 ± 0.8 pmol/L; P < 0.01) and AUC GIP dropped (2,524 ± 178 vs. 1,911 ± 162 [pmol/L] × min; P < 0.01), but fasting glucose (-0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L), and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] × min) remained unchanged. CONCLUSIONS: In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.

Relationship between plasma free fatty acid, intramyocellular triglycerides and long-chain acylcarnitines in resting humans.

We hypothesized that plasma non-esterified fatty acids (NEFA) are trafficked directly to intramyocellular long-chain acylcarnitines (imLCAC) rather than transiting intramyocellular triglycerides (imTG) on the way to resting muscle fatty acid oxidation. Overnight fasted adults (n = 61) received intravenous infusions of [U-(13)C]palmitate (0400-0830 h) and [U-(13)C]oleate (0800-1400 h) labelling plasma NEFA, imTG, imLCAC and im-non-esterified FA (imNEFA). Two muscle biopsies (0830 and 1400 h) were performed following 6 h, overlapping, sequential palmitate/oleate tracer infusions. Enrichment of plasma palmitate was approximately 15 times greater than enrichment of imTG, imNEFA-palmitate and im-palmitoyl-carnitine. Fatty acid enrichment in LCAC was correlated with imTG and imNEFA; there was a significant correlation between imTG concentrations and imLCAC concentrations in women (r = 0.51, P = 0.005), but not men (r = 0.30, P = 0.11). We estimated that approximately 11% of NEFA were stored in imTG. imTG NEFA storage was correlated only with NEFA concentrations (r = 0.52, P = 0.004) in women and with V(O(2),peak) (r = 0.45, P = 0.02) in men. At rest, plasma NEFA are trafficked largely to imTG before they enter LCAC oxidative pools; thus, imTG are an important, central pool that regulates the delivery of fatty acids to the intracellular environment. Factors relating to plasma NEFA storage into imTG differ in men and women.

A Self-Regulation-Based eHealth and mHealth Intervention for an Active Lifestyle in Adults With Type 2 Diabetes: Protocol for a Randomized Controlled Trial.

BACKGROUND: Adoption of an active lifestyle plays an important role in the management of type 2 diabetes. Online interventions targeting lifestyle changes in adults with type 2 diabetes have provided mixed results. Previous research highlights the importance of creating theory-based interventions adapted to the population's specific needs. The online intervention "MyPlan 2.0" targets physical activity and sedentary behavior in adults with type 2 diabetes. This intervention is grounded in the self-regulation framework and, by incorporating the feedback of users with type 2 diabetes, iteratively adapted to its target population. OBJECTIVE: The aim of this paper is to thoroughly describe "MyPlan 2.0" and the study protocol that will be used to test the effectiveness of this intervention to alter patients' levels of physical activity and sedentary behavior. METHODS: A two-arm superiority randomized controlled trial will be performed. Physical activity and sedentary behavior will be measured using accelerometers and questionnaires. Furthermore, using questionnaires and diaries, patients' stressors and personal determinants for change will be explored in depth. To evaluate the primary outcomes of the intervention, multilevel analyses will be conducted. RESULTS: The randomized controlled trial started in January 2018. As participants can start at different moments, we aim to finish all testing by July 2019. CONCLUSIONS: This study will increase our understanding about whether and how a theory-based online intervention can help adults with type 2 diabetes increase their level of physical activity and decrease their sedentary time. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12413.

Insulin resistance associates with hepatic lobular inflammation in subjects with obesity.

PURPOSE: Obese subjects with nonalcoholic fatty liver disease (NAFLD) are more prone to develop additional metabolic disturbances such as systemic insulin resistance (IR) and type 2 diabetes. NAFLD is defined by hepatic steatosis, lobular inflammation, ballooning and stage of fibrosis, but it is unclear if and which components could contribute to IR. OBJECTIVE: To assess which histological components of NAFLD associate with IR in subjects with obesity, and if so, to what extent. METHODS: This cross-sectional study included 78 obese subjects (mean age 46 ± 11 years; BMI 42.2 ± 4.7 kg/m2). Glucose levels were analysed by hexokinase method and insulin levels with electrochemiluminescence. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) was calculated. Liver biopsies were evaluated for histological components of NAFLD. RESULTS: A positive association between overall NAFLD Activity Score and HOMA-IR was found (r s = 0.259, P = 0.022). As per individual components, lobular inflammation and fibrosis stage were positively associated with HOMA-IR, glucose and insulin levels (P < 0.05), and HOMA-IR was higher in patients with more inflammatory foci or higher stage of fibrosis. These findings were independent of age, BMI, triglyceride levels, diabetes status and sex (all P < 0.043). In a combined model, lobular inflammation, but not fibrosis, remained associated with HOMA-IR. CONCLUSION: In this group of obese subjects, a major contributing histological component of NAFLD to the relation between NAFLD severity and IR seems to be the grade of hepatic lobular inflammation. Although no causal relationship was assessed, preventing or mitigating this inflammatory response in obesity might be of importance in controlling obesity-related metabolic disturbances.

Influence of Educational Level on Psychosocial Correlates and Perceived Environmental Correlates of Physical Activity in Adults at Risk for Type 2 Diabetes: The Feel4Diabetes-Study.

BACKGROUND: This study aimed to investigate whether the relationship between psychosocial and perceived environmental factors and physical activity (PA) in adults at risk for type 2 diabetes is influenced by educational level. METHODS: Based on the Finnish Diabetes Risk Score questionnaire, this study selected 164 adults (Mage: 38 (5.34) y, 13.4% men) at type 2 diabetes risk from 11 low socioeconomic neighborhoods in Flanders (Belgium). Participants filled out questionnaires on psychosocial and perceived environmental factors and wore an ActiGraph accelerometer for 5 consecutive days. Statistical analyses were performed using analysis of covariance in SPSS. RESULTS: Educational level significantly influenced the association between perception of body weight and light PA (P = .01) and total PA (P = .03) on weekend days. Educational level did not influence the associations between other psychosocial and perceived environmental factors (ie, perceived social influence; environmental, time and attitudinal barriers, perceived self-efficacy; knowledge and fatalism) and PA. CONCLUSIONS: Educational level did not influence the relationship between most psychosocial and perceived environmental factors and PA in this sample of adults at type 2 diabetes risk. This suggests that addressing different psychosocial and perceived environmental correlates in lower and higher educated participants might not be necessary. However, more research in this specific population is needed.

Experiences and Opinions of Adults with Type 2 Diabetes Regarding a Self-Regulation-Based eHealth Intervention Targeting Physical Activity and Sedentary Behaviour.

Background: Online interventions targeting a healthy lifestyle in adults with type 2 diabetes are more effective when informed by behaviour change theories. Although these theories provide guidance in developing the content of an intervention, information regarding how to present this content in an engaging way is often lacking. Consequently, incorporating users’ views in the creation of eHealth interventions has become an important target. Methods: Via a qualitative interview study with 21 adults with type 2 diabetes who had completed an online self-regulation-based intervention (‘MyPlan 2.0’), we assessed participants’ opinions regarding the usefulness of the implemented self-regulation techniques, the design of the programme as well as their knowledge regarding physical activity and sedentary behaviour. A directed content analysis was performed to synthesize the interview data. Results: Participants experienced difficulties completing the coping planning component. The simple design of the website was considered helpful, and most participants were aware of the beneficial effects of an active lifestyle. Conclusions: ‘MyPlan 2.0’ was well-accepted by the majority of participants. However, the coping planning component will need to be adapted. Based on these findings, recommendations on how to tailor eHealth interventions to the population of adults with type 2 diabetes have been formulated.