Decline in HbA1c during the first year of elexacaftor/tezacaftor/ivacaftor treatment in the Danish cystic fibrosis cohort: Short title: Decline in HbA1c after elexacaftor/tezacaftor/ivacaftor treatment.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI. METHODS: We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study. HbA1c was measured at baseline, 3, 6, 9 and 12 months after treatment initiation. Change in HbA1c was assessed in mixed models adjusted for age, sex, glucose tolerance and prior CFTR modulator treatment. In a sub-population with CFRD, we assessed the change in insulin usage, hypoglycemic events and the 30-day continuous glucose monitoring (CGM) parameters (i.e., average blood glucose, time below (≤3.9 mM) and above (>10.0 mM) normal range, and the variation in glucose) after 12 months of treatment. RESULTS: Among 321 individuals with CF, HbA1c declined by 2.1 mmol/mol [95 % confidence interval (CI): -2.6; -1.5 mmol/mol] after 3 months and by 2.3 mmol/mol [95 %CI: -2.8; -1.9 mmol/mol] after 12 months of ETI treatment. The decline was independent of glucose tolerance status at baseline. In 26 individuals with CFRD at baseline, the mean decline in HbA1c was 3.6 mmol/mol [95 %CI: -6.9; -0.4 mmol/mol] after 12 months, but we did not observe any change in insulin usage, weekly number of hypoglycemic events or CGM parameters. CONCLUSION: In the Danish CF cohort, HbA1c declined over 12 months of ETI treatment, however, among a subset with CFRD, we observed no change in insulin usage and CGM glucose levels.

Cardiac arrhythmia and hypoglycaemia in patients receiving haemodialysis with and without diabetes (the CADDY study): protocol for a Danish multicentre cohort study.

INTRODUCTION: Patients receiving haemodialysis are at increased risk of arrhythmias and sudden cardiac death, but data on arrhythmia burden and the pathophysiology remain limited. Among potential risk factors, hypoglycaemia is proposed as a possible trigger of lethal arrhythmias. The development of implantable loop recorders (ILR) and continuous glucose monitoring (CGM) enables long-term continuous ECG and glycaemic monitoring. The current article presents the protocol of a study aiming to increase the understanding of arrhythmias and risk factors in patients receiving haemodialysis. The findings will provide a detailed exploration of the burden and nature of arrhythmias in these patients including the potential association between hypoglycaemia and arrhythmias. METHODS AND ANALYSIS: The study is an investigator-initiated, prospective, multicentre cohort study recruiting 70 patients receiving haemodialysis: 35 with diabetes and 35 without diabetes. Participants are monitored with ILRs and CGM for 18 months follow-up. Data collection further includes a monthly collection of predialysis blood samples and dialysis parameters. The primary outcome is the presence of clinically significant arrhythmias defined as a composite of bradycardia, ventricular tachycardia, or ventricular fibrillation. Secondary outcomes include the characterisation of clinically significant arrhythmias and other arrhythmias, glycaemic characteristics, and mortality. The data analyses include an assessment of the association between arrhythmias and hypoglycaemia and hyperglycaemia, baseline clinical variables, and parameters related to kidney failure and the haemodialysis procedure. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the Capital Region of Denmark (H-20069767). The findings will be presented at national and international congresses as well as in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04841304.

Co-creating active communities: processes and outcomes of linking public rehabilitation programs with civic engagement for active living in a Danish municipality.

BACKGROUND: Increased levels of physical activity are associated with beneficial health effects for people with type 2 diabetes, cardiovascular disease and/or severe obesity; however, transforming knowledge about these effects into action is challenging. The aim of this paper is to explore lessons learnt from a co-creation process in a partnership project involving local stakeholders, including citizens, and researchers. The purpose of the process was to link a public health care institution with civil society organisations in the local community to make it possible for citizens to continue to be physically active after ending their public rehabilitation. Secondarily, this paper aims to develop a conceptual model of the above process. METHODS: The study constitutes the first part of Project Active Communities and was based on a partnership between three research institutions and a Danish rural municipality, involving municipal and civil society stakeholders and citizens with type 2 diabetes, cardiovascular disease and/or severe obesity in co-creation of concrete interventions for implementation. The co-creation process was divided into two tracks, one involving citizens (two workshops) and one involving municipal and civil society stakeholders (two workshops). The two tracks were concluded with a final workshop involving all stakeholders, including local politicians. Data sources are focus groups and bilateral meetings, workshop observations, and questionnaires. RESULTS: Lessons learnt include the importance of having a flexible timeframe for the co-creation process; giving room for disagreements and matching of mutual expectations between stakeholders; the value of a coordinator in the municipality to achieve acceptance of the project; and the significance of engaging local politicians in the co-creation process to accommodate internal political agendas. We have developed a conceptual model for a co-creation process, where we outline and explain three distinct phases: stakeholder identification and description, co-creation, and prototyping. The model can be adapted and applied to other sectors and settings. CONCLUSIONS: This study documents lessons learnt in a co-creation process aiming to link a public health care institution with civil society organisations in the local community. Further, this study has specified productive co-creative processes and documented the various phases in a conceptual model.

It is well known that physical activity has health benefits for people with chronic diseases. In this study, our aim was to explore lessons learnt from a co-creation process and develop a model for others to apply. The study was based on a partnership between three research institutions and a Danish rural municipality, involving municipal and civil society stakeholders and citizens with type 2 diabetes, cardiovascular disease and/or severe obesity. During the study, the above-mentioned stakeholders were invited to five workshops, where interventions for linking a public health care institution and civil society organisations were co-created. The five co-creation workshops led to the identification of four interventions, linking public health care institutions and civil society organisations. Lessons learnt from this project, which can be used by others who wish to design and conduct a co-creative process with diverse stakeholders, include: the importance of having a flexible timeframe for the co-creation process, as delays can easily occur in the unpredictable process of co-creation giving room for disagreements and matching of mutual expectations between stakeholders, as a common understanding of each stakeholder's motives is important for the success of the project the importance and value of a coordinator in the municipality to achieve acceptance of the project the significance of engaging local politicians in the co-creation process to take internal political agendas into consideration. We conclude by identifying three phases­a stakeholder, a co-creation, and a prototyping phase­in a model for co-creation that may be adapted and used by others.

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

Aims: The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment. Methods: Adults with CF (≥18 years) were included in a cross-sectional study using an extended (-10, -1, 10, 20, 30, 45, 60, 90, 120, 150, and 180 min) or a standard (-1, 30, 60, and 120 min) oral glucose tolerance test (OGTT). Participants were classified according to glucose tolerance status and hypoglycaemia was defined as 3-hour glucose <3.9 mmol/L in those with normal glucose tolerance (NGT) and early glucose intolerance (EGI). Results: Among 93 participants, 67 underwent an extended OGTT. In addition to worsening in insulin secretion, the progression to CFRD was associated with signs of beta cell stress, as the fasting proinsulin-to-insulin ratio incrementally increased (p-value for trend=0.013). The maximum proinsulin level (pmol/L) was positively associated with the nadir glucagon, as nadir glucagon increased 6.2% (95% confidence interval: 1.4-11.3%) for each unit increase in proinsulin. Those with hypoglycaemia had higher 60-min glucose, 120-min C-peptide, and 180-min glucagon levels (27.8% [11.3-46.7%], 42.9% [5.9-92.85%], and 80.3% [14.9-182.9%], respectively) and unaltered proinsulin-to-insulin ratio compared to those without hypoglycaemia. Conclusions: The maximum proinsulin concentration was positively associated with nadir glucagon during the OGTT, suggesting that beta cell stress is associated with abnormal alpha cell function in adults with CF. In addition, hypoglycaemia seemed to be explained by a temporal mismatch between glucose and insulin levels rather than by an impaired glucagon response.

Effects of different doses of exercise in adjunct to diet-induced weight loss on the AGE-RAGE axis in patients with short standing type 2 diabetes: Secondary analysis of the DOSE-EX multi-arm, parallel-group, randomised trial.

AIMS/HYPOTHESIS: These secondary analyses aimed to investigate the effects of different volumes of exercise in adjunct to diet-induced weight loss and standard care on advanced glycation end-products (AGEs) and receptor for AGE (RAGE). We hypothesized that exercise in adjunct to a diet-induced weight loss would dose-dependently increase the soluble decoy receptor for AGE (sRAGE) more than diet-induced weight loss and standard care alone. Secondarily, we expected changes in sRAGE to be associated with improved glycaemic control and inversely associated with low-grade inflammation. METHODS: The DOSE-EX study was a 16-week parallel-group, 4-arm, single-centre, assessor-blinded, randomised, controlled trial (NCT03769883). We included persons living with T2D, duration ≤7 years, BMI >27 kg/m2 and <40 kg/m2, without severe diabetic complications. Participants were randomised (1:1:1:1) to either 1) standard care as control (CON), 2) standard care + diet (DCON), 3) standard care + diet + moderate exercise dose (MED) or 4) standard care + diet + high exercise dose (HED). Standard care included algorithm-guided pharmacological treatment. The diet intervention aimed at 25% reduced energy intake. The supervised exercise sessions included two aerobic sessions + one combined (aerobic and resistance training) session per week for the MED group, and four aerobic sessions + two combined sessions per week for the HED group. Primary outcome was the change in sRAGE from baseline to 16-week follow-up. Secondary outcomes encompassed changes in advanced glycation endproducts (AGE), glycaemic control and markers of low-grade inflammation. RESULTS: A total of 80 participants (CON: n = 20, DCON: n = 19, MED: n = 20, HED: n = 21) were included in this secondary analysis. The mean age was 58.3 years (SD 9.9), 53% males, and median T2D duration was 4.1 years (IQR 2.0-5.5). No change in sRAGE was observed in any of the groups from baseline to follow-up (p > 0.05). CONCLUSION/INTERPRETATION: A 16-week intervention with either three or six exercise sessions per week in adjunct to diet-induced weight loss did not change the levels of sRAGE in persons living with well-regulated, short standing T2D.

Changes in glucose tolerance in people with cystic fibrosis after initiation of first-generation CFTR modulator treatment.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to have a beneficial effect on pulmonary function and nutritional status in patients with cystic fibrosis (CF), but the extent to which they affect glucose tolerance is not fully understood. In the current study, we evaluated the change in glucose tolerance and insulin secretion after first-generation CFTR modulator treatment in adults with CF. METHODS: We performed a longitudinal observational study with an oral glucose tolerance test performed at baseline and after three and a half years of follow-up. The test comprised glucose, C-peptide and insulin measured at fasting, 1 h, and 2 h, and HbA1c at fasting. We compared changes in parameters of glucose tolerance and insulin secretion from baseline to follow-up. RESULTS: Among 55 participants, 37 (67%) were treated with a first-generation CFTR modulator for a median of 21 months. Glucose levels were unchanged in both the treated and untreated group. In the treated group, C-peptide levels declined, yet no significant differences in glucose, insulin, and C-peptide levels were observed between the groups. HbA1c increased in both groups, while no significant change in the insulin sensitivity indices was detected in either group. However, homeostatic model assessment for insulin resistance tended to decline in the treated group, whilst tending towards an increase in the untreated group. The difference between the groups reached statistical significance (p = 0.040). CONCLUSION: Treatment with first-generation CFTR modulators, mainly tezacaftor/ivacaftor, did not seem to be associated with glucose tolerance nor insulin secretion in adults with CF. However, CFTR modulators may still have a beneficial effect on insulin sensitivity.

Cardiovascular mortality in patients with advanced chronic kidney disease with and without diabetes: a nationwide cohort study.

BACKGROUND: Cardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels. METHODS: In a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate < 30 mL/min/1.73m2 between 2002 and 2018. Patients with advanced CKD were age- and sex-matched with four individuals from the general Danish population. Cause-specific Cox regression models were used to estimate the 1-year risk of cardiovascular mortality standardized to the distribution of risk factors in the cohort. RESULTS: We included 138,583 patients with advanced CKD of whom 32,698 had diabetes. The standardized 1-year risk of cardiovascular mortality was 9.8% (95% CI 9.6-10.0) and 7.4% (95% CI 7.3-7.5) for patients with and without diabetes, respectively, versus 3.1% (95% CI 3.1-3.1) in the matched cohort. 1-year cardiovascular mortality risks were 1.1- to 2.8-fold higher for patients with diabetes compared with those without diabetes across the range of advanced CKD stages and age groups. Albuminuria and anemia were associated with increased cardiovascular mortality risk regardless of diabetes status. LDL-cholesterol was inversely associated with cardiovascular mortality risk in patients without diabetes, while there was no clear association in patients with diabetes. CONCLUSIONS: Diabetes, albuminuria, and anemia remained important risk factors of cardiovascular mortality whereas our data suggest a limitation of LDL-cholesterol as a predictor of cardiovascular mortality in advanced CKD.

Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment.

BACKGROUND: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is 'weak against'. OBJECTIVES: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. METHODS: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5-50 mg, THC 2.5-25 mg, and CBD/THC 5 mg/2.5 mg-50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. RESULTS: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04-0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11-2.19), THC 0.38 (CI -0.65 to 1.4) and CBD/THC -0.12 (-1.13 to 0.89). CONCLUSIONS: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.

Micro- and macrovascular complications and risk factors for foot ulceration and amputation in individuals receiving dialysis with and without diabetes.

INTRODUCTION: This study examined the prevalence of microvascular and macrovascular complications in people receiving dialysis with and without diabetes and investigated independent risk factors for foot ulcers and lower-extremity amputations. METHODS: We performed a cross-sectional study of 119 individuals with diabetes and 219 individuals without diabetes receiving chronic dialysis during June 2019 at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Effects of diabetes and other risk factors were assessed by log-binomial regression. Prevalence data were compared with a historical control group of 38 individuals with diabetes receiving dialysis examined in 2004 in the same department. RESULTS: We found that persons with diabetes had a twofold higher risk ratio of current (unadjusted risk ratio 2.2 [95% CI 1.1, 4.7]) and previous foot ulcer (2.5 [1.7, 3.7]) and a fourfold higher risk ratio of lower-extremity amputation (4.2 [2.1, 8.6]) in comparison with persons without diabetes (all p < .05). Furthermore, persons with diabetes had a 70% increased risk ratio of myocardial infarction (1.7 [1.0-2.8], p = .041). In multivariable-adjusted analysis, current foot ulcer was independently associated with previous foot ulcer (adjusted risk ratio 4.0 [95% CI 1.8, 8.9]), while lower-extremity amputation was independently associated with diabetes (3.8 [1.8, 8.2]) and male sex (4.1 [1.5, 11.3]) (all p < .01). CONCLUSIONS: Individuals with diabetes receiving dialysis had a higher prevalence of foot ulcer, lower-extremity amputation and myocardial infarction compared to individuals without diabetes. Previous foot ulcer was the most important risk factor for current foot ulcer, while diabetes and male sex were important risk factors for lower-extremity amputation.

Associations Between Glucose Tolerance, Insulin Secretion, Muscle and Fat Mass in Cystic Fibrosis.

BACKGROUND: A frequent comorbidity in cystic fibrosis (CF) is CF related diabetes (CFRD) caused by a gradual decline in insulin secretion. The reduction in the anabolic hormone, insulin, might explain the weight loss that precedes onset of CFRD. We investigated the association between muscle and fat mass in relation to glucose tolerance and insulin function. METHODS: In a cross-sectional study with CF patients (⩾18 years), we conducted an oral glucose tolerance test and dual energy X-ray absorptiometry scan (DXA). Based on plasma glucose, glucose tolerance was defined as normal (NGT): 1-hour <11.1 mmol/L and 2-hour <7.8 mmol/L, impaired (IGT): 2-hour ⩾7.8 and <11.1 mmol/L or CFRD: 2-hour ⩾11.1 mmol/L. Insulin resistance (HOMA-IR) was derived from fasting levels of plasma glucose and plasma insulin, and fat-free and fat mass index (kg/m2) from DXA. Associations were evaluated using linear regression models adjusted for age, sex, and pancreas insufficiency. RESULTS: Among 79 CF patients with exocrine pancreas insufficiency, impairment of glucose tolerance corresponded to reduced insulin secretion. In the IGT group the fat-free mass index (FFMI) was 1.2 kg/m2 (95% CI: [-2.3, -0.03] kg/m2, P = .044) lower compared to the NGT group. FFMI increased insignificantly by 0.4 kg/m2 (95% CI: [-0.6, 1.5] kg/m2, P = .422) among the insulin-treated CFRD group compared to IGT. Fat mass index (FMI) was not different between groups but tended to decrease with glucose tolerance impairment. For each 100 pmol/L increase in fasting insulin FFMI increased by 1.77 kg/m2 (95% CI: [0.21, 3.33] kg/m2/pmol/L/100) and FMI increased by 6.15 kg/m2 (95% CI: [3.87, 8.44] kg/m2/pmol/L/100). In multivariate analyses, HOMA-IR was positively associated with FFMI (ß = 0.5 kg/m2/HOMA-IR, 95% CI: [0.08, 0.92] kg/m2/HOMA-IR, P = .021) and FMI (ß = 1.5 kg/m2/HOMA-IR, 95% CI: [0.87, 2.15] kg/m2/HOMA-IR, P < .001). CONCLUSIONS: Muscle mass was significantly lower among participants with impaired glucose tolerance (IGT), while muscle mass was normalized among those treated with insulin.

Study rationale and design of the EANITIATE study (EmpAgliflozin compared to NPH Insulin for sTeroId diAbeTEs) - a randomized, controlled, multicenter trial of safety and efficacy of treatment with empagliflozin compared with NPH-insulin in patients with newly onset diabetes following initiation of glucocorticoid treatment.

BACKGROUND: A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes. METHODS: EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose-Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded continuous glucose monitoring (CGM) will provide data for the primary endpoint (mean daily blood glucose) and on glucose fluctuations in the two treatment arms. Secondary endpoints are patient related outcomes, hypoglycaemia, means and measures of variation for all values and for time specific glucose values. This is a non-inferiority study with the intent to demonstrate that treatment with empagliflozin is not inferior to treatment with NPH insulin when it comes to glycemic control and side effects. DISCUSSION: This novel approach to management of glucocorticoid-induced hyperglycemia has not been tested before and if SGLT2 inhibition with empaglifozin compared to NPH-insulin is a safe, effective and resource sparing treatment for GIDM, it has the potential to improve the situation for affected patients and have health economic benefits. TRIAL REGISTRATION: www.clinicaltrialsregister.eu no.: 2018-002640-82. Prospectively registered November 20th. 2018. Date of first patient enrolled: June 4th. 2019. This protocol article is based on the EANITATE protocol version 1.3, dated 29. January 2018.

Effect of Metformin vs. Placebo in Combination with Insulin Analogues on Bone Markers P1NP and CTX in Patients with Type 2 Diabetes Mellitus.

Preclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and insulin before entering the study. Bone formation and resorption were assessed by measuring, N-terminal propeptide of type I procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) at baseline and end of study. The influence of gender, age, smoking, body mass index (BMI), T2DM duration, glycosylated hemoglobin A1c (HbA1c), c-reactive protein (CRP) and insulin dosage was also included in the analyses. The levels of bone formation marker P1NP and bone resorption marker CTX increased significantly in both groups during the trial. P1NP increased less in the Metformin + Insulin compared to the placebo + insulin group (p = 0.001) (between group difference change), while the increases in CTX levels (p = 0.11) were not different. CRP was inversely associated (p = 0.012) and insulin dosage (p = 0.011) was positively related with change in P1NP levels. BMI (p = 0.002) and HbA1C (p = 0.037) were inversely associated with change in CTX levels. During 18 months of treatment with metformin or placebo, both in combination with insulin, bone turnover increased in both groups. But the pattern was different as the bone formation marker (P1NP) increased less during Metformin + Insulin treatment, while change in bone resorption (CTX) was not significantly different between the two groups.

Dietary habits and adherence to dietary recommendations in patients with type 1 and type 2 diabetes compared with the general population in Denmark.

OBJECTIVES: The aim of the present study was to examine dietary habits and adherence to dietary recommendations in adult patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) compared with the general population in Denmark. METHODS: The study was cross-sectional and included 426 patients with T1D and 348 patients with T2D recruited from an outpatient diabetes clinic in the capital region of Denmark. Dietary habits were assessed by a food frequency questionnaire and compared with dietary data from 2,899 participants without diabetes from the Danish National Survey of Dietary Habits and Physical Activity. RESULTS: Patients with diabetes had a 20-50% lower intake of added sugar and alcohol, and a 10-20% higher intake of fibre and vegetables compared with the general population (p<0.001 for all). Patients with T2D had a 37% lower intake of alcohol compared with T1D (p<0.001). Adherence to dietary recommendations (e.g. fibre, saturated fat, vegetables, fruit and fish) were low in all groups but lowest in the general population. CONCLUSION: The Danish diet is too high in saturated fat and too low in dietary fibre, vegetable, fruit and fish compared to dietary recommendations in both patients with diabetes and the general population. However, our data demonstrate that patients with diabetes consume a healthier diet compared to the general population: Limiting the intake of added sugar and alcohol, and increasing the intake of vegetables and dietary fibre.

Prevalence of micro- and macrovascular diabetes complications at time of type 2 diabetes diagnosis and associated clinical characteristics: A cross-sectional baseline study of 6958 patients in the Danish DD2 cohort.

AIMS: To examine the prevalence of micro- and macrovascular complications and their associated clinical characteristics at time of type 2 diabetes (T2D) diagnosis. METHODS: We examined the prevalence of complications and associated clinical characteristics among 6958 newly diagnosed T2D patients enrolled in the prospective Danish Center for Strategic Research in T2D cohort during 2010-2016. We calculated age- and gender-adjusted prevalence ratios (aPRs) of complications using log-binomial and Poisson regression. RESULTS: In total, 35% (n=2456) T2D patients had diabetic complications around diagnosis; 12% (n=828) had microvascular complications, 17% (n=1186) macrovascular complications, and 6% (n=442) had both. HbA1c levels of ≥7% were associated with microvascular complications [HbA1c 7%-8%; aPR: 1.35, 95% confidence interval (CI): 1.12-1.62] but not macrovascular complications [aPR: 0.91, 95% CI: 0.76-1.08]. High C-peptide≥800pmol/L was associated with macrovascular [aPR 1.34, 95% CI: 1.00-1.80] but not microvascular [aPR 0.97, 95% CI: 0.71-1.33] complications. Macrovascular complications were associated with male sex, age>50years, obesity, hypertriglyceridemia, low HDL cholesterol, smoking, elevated CRP levels, and anti-hypertensive therapy. Microvascular complications were associated with high blood pressure, hypertriglyceridemia, and absence of lipid-lowering therapy. CONCLUSIONS: One-third of patients with T2D had diabetes complications around time of diagnosis. Our findings suggest different pathophysiological mechanisms behind micro- and macrovascular complications.

Prevalence of type 2 diabetes mellitus complications among palestinians with T2DM.

AIMS: To assess the prevalence of microvascular and macrovascular complications of type 2 diabetes (T2DM) among Palestinians. METHODS: 1308 diagnosed T2DM attending four main Primary Health Care Clinics on the Southern West Bank of Palestine examined by a Mobile Diabetes Clinic team. All diabetes patients visiting the clinics during a one-month period for each clinic were included. Interviews, anthropometric measurements, physical examination, and laboratory tests: HbA1c, lipid profile, and kidney function tests analyzed in a central laboratory were obtained RESULTS: 1308 diabetes patients, including 839 females (64%), with a mean age of 57 years (SD=8.7), and mean diabetes duration 7.1 years(SD=6.25), participated. 95.3% presented as overweight (BMI >25kg/m2) or obese (BMI>30kg/m2) with mean BMI of 33.46 (SD=5.95). The mean HbA1c (tested in 1221 patients) was 9.21(SD=2). Only 16.1% had HbA1c <7.0%. Hypertension (blood pressure>140/90mmHg) were found in 23%, and dyslipidemia (total cholesterol>200mg/dl) was present in 37.3% of patients. 213(16.3%) had a history of the macrovascular disease (previous myocardial infarction or stroke), and 290 (25.9%) had microvascular complications. Moreover, 40 (4.9%) had advanced kidney disease with serum creatinine>1.4mg/dl. CONCLUSIONS: The present cross-sectional study shows poor glycemic control in Palestine, while blood pressure and lipids are less poorly controlled. The study emphasizes the need to optimize the glucose-lowering treatment and to implement diabetes care program that could face the challenge of high uncontrolled diabetes as well as complications of diabetes.

Prediction of excessive weight gain in insulin treated patients with type 2 diabetes.

BACKGROUND: Weight gain is an ongoing challenge when initiating insulin therapy in patients with type 2 diabetes mellitus (T2DM). However, if prediction of insulin-associated weight gain was possible on an individual level, targeted initiatives could be implemented to reduce weight gain. The aim of the present study was to identify predictors of weight gain in insulin-treated patients with T2DM. METHODS: In all, 412 individuals with T2DM were, in addition to metformin or placebo, randomized into 18-month treatment groups with three different insulin analog treatment regimens (biphasic, aspart, detemir). Participants with excessive weight gain were defined as the group with weight gain in the 4th quartile (>6.2 kg).We developed a pattern classification method to predict individuals prone to excessive weight gain. RESULTS: Over the 18-month treatment period, median weight gain among all 412 patients was 2.4 kg (95% prediction interval [PI] -5.6, 12.4 kg), whereas median weight gain for those in the upper 4th quartile (n = 103) was 8.9 kg (95% PI 6.3, 15.2 kg). No clinical baseline data were strong predictors of excessive weight gain. However, the weight gain during the first 3 months of the trial and the subsequent dose of insulin yielded a useful predictor for weight gain at the 18-month follow-up. Combining these two predictors into a prediction model with other clinical available information produced a receiver operating characteristic area under the curve of 0.80. CONCLUSIONS: We have developed a prediction model that could help identify a substantial proportion of individuals with T2DM prone to large weight gain during insulin therapy.

Associations of objectively measured physical activity and abdominal fat distribution.

INTRODUCTION/PURPOSE: Visceral adipose tissue (VAT) and physical activity are both independent predictors of Type 2 diabetes. Physical activity and overall obesity are inversely associated with each other. Yet the nature of the association between objectively measured dimensions of physical activity and abdominal fat distribution has not been well characterized. We aimed to do so in a middle-age to elderly population at high risk of diabetes. METHODS: A cross-sectional analysis of 1134 participants of the ADDITION-PRO study. VAT and subcutaneous adipose tissue (SAT) were assessed one-dimensionally by ultrasonography and physical activity with combined accelerometry and HR monitoring. Linear regression of physical activity energy expenditure (PAEE) and time spent in different physical activity intensity levels on VAT and SAT was performed. RESULTS: Median body mass index (BMI) was 26.6 kg·m and PAEE was 28.1 kJ·kg·d, with 18.9 h·d spent sedentary, 4.5 h·d in light-intensity physical activity, and 0.4 h·d in moderate-intensity physical activity. PAEE was significantly negatively associated with VAT, and in women, PAEE was also significantly negatively associated with SAT. The difference in VAT was -1.1 mm (95% confidence interval [CI] = -1.8 to -0.3) per 10-kJ·kg·d increment, and the corresponding difference in SAT for women was -0.6 mm (95% CI = -1.2 to -0.04) in models adjusted for age, sex, and waist circumference. Exchanging 1 h of light physical activity with moderate physical activity was significantly associated with VAT (-4.5 mm, 95% CI = -7.6 to -1.5). Exchanging one sedentary hour with light physical activity was significantly associated with both VAT (-0.9 mm, 95% CI = -0.1 to -1.8) and SAT (-0.4 mm, 95% CI = -0.0 to -0.7). CONCLUSIONS: In this population with low physical activity levels, cross-sectional findings indicate that increasing overall physical activity and decreasing time spent sedentary is important to avoid the accumulation of metabolically deleterious VAT.

Improved survival among patients with complicated type 2 diabetes in Denmark: a prospective study (2002-2010).

CONTEXT: It is unclear to what extent recent advances in diabetes care have reduced the excess mortality in patients with complicated type 2 diabetes. OBJECTIVE: The aim of this study was to estimate time trends in mortality among patients with complicated type 2 diabetes at the Steno Diabetes Center relative to the general Danish background population. DESIGN, SETTING, AND STUDY PARTICIPANTS: We performed a longitudinal follow-up study from 2002 to 2010 of 5844 patients with type 2 diabetes at the Steno Diabetes Center, Denmark. All-cause and cause-specific mortality was identified from the national death register. MAIN OUTCOME MEASURES: Poisson regression was used to model mortality rates by sex, age, age of diabetes onset, and calendar time. RESULTS: A total of 1341 deaths occurred (802 men and 539 women) during 32,913 person-years of follow-up. Total mortality rates in the diabetes population decreased by 5.5% (95% confidence interval 2.9%-8.0%) per year in men and by 3.3% (0.0%-6.4%) per year in women. Among men but not women, this decline was significantly steeper than the decline in mortality in the Danish background population (men, -3.0% [-5.6% to -0.4%]; women, -1.4 [-4.6% to 2.0%]). The decline in overall mortality was explained by a decline in cardiovascular mortality for both men and women. CONCLUSION: Overall and cardiovascular mortality have decreased during the last decade among Danish patients with complicated type 2 diabetes, and for men, the decline in mortality was more pronounced than in the general population.

Percutaneous flexor tenotomy for preventing and treating toe ulcers in people with diabetes mellitus.

INTRODUCTION: The purpose was to examine the effectiveness of flexor tenotomy in a modified technique to prevent and heal neuropathic and neuroischaemic pressure ulcers on the tip of the toe in claw- or hammer-toe deformities in people with diabetes. PATIENTS AND METHODS: A consequetive 4 years series of 38 patients was retrospectively studied. Percutaneous tenotomy on the superficial and deep flexor tendons was performed in 65 toes through a small transverse plantar stab incision just proximal to the web level. There were 16 (42%) patients with 27 ulcerated toes and 22 (58%) patients with 38 toes with impending ulceration. Ten patients had neuropathic ulcers and six patients had neuro-ischaemic ulcers. Sixteen patients (42%) had macrovascular disease. Ten (26%) had proliferative rethinopathy, 7 (18%) macroalbuminuria and 18 (47%) microalbuminuria. RESULTS: All surgical incisions healed uneventfully. Twenty-five (93%) of the toe ulcers healed in median 21 days (range 7-224 days). Three patients had recurrence of the ulcer. There were no infections in the incisions or toe amputations. No patients treated with preventive tenotomy experienced toe ulceration. No complications were recorded in neuro-ischaemic ulcers. During the follow up period of median 31 months (range 2-48 months) 33 other ulcers were recorded in 18 patients (47%). One of these developed a transfer ulceration under the adjacent metatarso-phalangeal joint and another had a late pressure ulcer on a neighbouring toe. The other 31 ulcers were not related to ulcers treated with tenotomy. CONCLUSION: Tenotomy is a simple, safe and effective procedure for preventing and treating distal plantar neuropathic toe ulcers in claw toe or hammer toe deformities in people with diabetes with or without serious co-morbidity. The results suggest that tenotomy should be considered also in neuroischaemic ulcers.