Diabetic Retinopathy in Newly Diagnosed Subjects With Type 2 Diabetes Mellitus: Contribution of β-Cell Function

Purpose: The association of hyperglycemia and diabetic retinopathy (DR) in established type 2 diabetes mellitus (T2DM) subjects is well accepted. However, the association between β-cell responsiveness and insulin sensitivity leading to fasting and postprandial hyperglycemia with DR in newly diagnosed treatment-naïve T2DM subjects remain unreported. Methods: A total of 544 newly diagnosed treatment-naïve T2DM subjects were screened for DR (digital photography) and underwent a standardized meal tolerance test. Serial plasma glucose and insulin levels were measured, and fasting (M0) and postprandial β-cell responsiveness calculated Calculating Pancreatic Response Program along with homeostasis model assessment-β cell function (HOMA-B) and HOMA-Insulin Sensitivity. A subgroup of 201 subjects also underwent a frequently sampled IV glucose tolerance test and the acute insulin response to glucose, insulin sensitivity, and glucose effectiveness (SG) estimated (MINMOD model). Results: A total of 16.5% (90) subjects had DR at diagnosis. Subjects with DR had significantly reduced M0, HOMA-B and SG leading to higher fasting and postprandial (2 hour) glucose and significantly lower fasting and postprandial (2 hour) insulin. Factors independently associated with DR in multivariate logistic regression analysis were M0, HOMA-B, and SG with fasting and postprandial (2 hour) glucose and insulin. There was no statistical difference in glycated hemoglobin, systolic blood pressure, acute insulin response to glucose, and insulin sensitivity between those with or without DR. Principal Conclusions: In this cohort of newly diagnosed T2DM subjects, DR is associated with reduced β-cell responsiveness, resulting from β-cell failure rather than insulin resistance, leading to fasting and postprandial hyperglycemia and hypoinsulinemi

Identifying all persons in Wales with type 1 diabetes mellitus using routinely collected linked data

Introduction Type 1 diabetes mellitus (T1DM) is an autoimmune condition characterised by hyperglycaemia, caused by the destruction of insulin producing β-cells in the pancreas. Previous epidemiological population level studies of T1DM and its complications have typically used recorded T1DM diagnoses to determine diabetes status and define cohorts. Objectives and Approach The objective was to identify all persons with T1DM in Wales from Primary (~70\% population coverage) and Secondary Care (100% coverage) data held in the Secure Anonymised Information Linkage (SAIL) databank. People with a coded T1DM diagnosis (using Read codes in Primary Care data and International Classification of Disease (ICD10) codes in Secondary Care data), plus either insulin prescribed shortly after diagnosis or a hospital admission for diabetic ketoacidosis were identified as having T1DM. A sub-group of this SAIL e-cohort were validated using a register of persons diagnosed with T1DM in Wales under 15 years old (Brecon cohort). Results 18,285 people had a T1DM diagnosis and 10,539 had more T1DM than type 2 diabetes mellitus (T2DM) diagnoses. 6,375 persons were identified with T1DM in Primary Care data using our criteria, with a median diagnosis age of 19.2 years (interquartile range 11.0, 35.5). 47.5\% were diagnosed under 18 years of age. 39.6% of people with a T1DM diagnosis did not have T1DM using our criteria. False positive and negative rates of 4.8% and 4.5% respectively were achieved by comparing persons in the SAIL e-cohort against the Brecon cohort. Clinician estimated false positive and negative rates were 1.4% and 3.9% respectively. The prevalence of T1DM in Wales in 2016 was 0.37% or 11,049 people. Conclusion/Implications Our criteria for identifying people with T1DM was more reliable than using diagnosis codes alone, allowing for a more accurate, efficient and reproducible means of identifying individuals with T1DM for researchers utilising the SAIL databank, and other national health repositories

A retrospective epidemiological study of Type 1 Diabetes Mellitus in Wales, UK between 2008 and 2018

Introduction Studies of prevalence and the demographic profile of type 1 diabetes are challenging because of the relative rarity of the condition, however, these outcomes can be determined using routine healthcare data repositories. Understanding the epidemiology of type 1 diabetes allows for targeted interventions and care of this life-affecting condition. Objectives To describe the prevalence, incidence and demographics of persons with type 1 diabetes diagnosed in Wales, UK, using the Secure Anonymised Information Linkage (SAIL) Databank. Methods Data derived from primary and secondary care throughout Wales available in the SAIL Databank were used to identify people with type 1 diabetes to determine the prevalence and incidence of type 1 diabetes over a 10 year period (2008–18) and describe the demographic and clinical characteristics of this population by age, socioeconomic deprivation and settlement type. The seasonal variation in incidence rates was also examined. Results The prevalence of type 1 diabetes in 2018 was 0.32% in the whole population, being greater in men compared to women (0.35% vs 0.28% respectively); highest in those aged 15-29 years (0.52%) and living in the most socioeconomically deprived areas (0.38%). The incidence of type 1 diabetes over 10 years was 14.0 cases/100,000 people/year for the whole population of Wales. It was highest in children aged 0-14 years (33.6 cases/100,000 people/year) and areas of high socioeconomic deprivation (16.8 cases/100,000 people/year) and least in those aged 45-60 years (6.5 cases/100,000 people/year) and in areas of low socioeconomic deprivation (11.63 cases/100,000 people/year). A seasonal trend in the diagnoses of type 1 diabetes was observed with higher incidence in winter months. Conclusion This nation-wide retrospective epidemiological study using routine data revealed that the incidence of type 1 diabetes in Wales was greatest in those aged 0-14 years with a higher incidence and prevalence in the most deprived areas. These findings illustrate the need for health-related policies targeted at high deprivation areas to include type 1 diabetes in their remit

Can HbA1c detect undiagnosed diabetes in acute medical hospital admissions?

Objective: to study hyperglycaemia in acute medical admissions to Irish regional hospital.Research design and methods: from 2005 to 2007, 2061 white Caucasians, aged &gt;18 years, were admitted by 1/7 physicians. Those with diabetes symptoms/complications but no previous record of hyperglycaemia (n = 390), underwent OGTT with concurrent HbA1c in representative subgroup (n = 148). Comparable data were obtained for 108 primary care patients at risk of diabetes.Results: diabetes was diagnosed immediately by routine practice in 1% (22/2061) [aged 36 (26–61) years (median IQ range)/55% (12/22) male] with pre-existing diabetes/dysglycaemia present in 19% (390/2061) [69 (58–80) years/60% (235/390) male].Possible diabetes symptoms/complications were identified in 19% [70 (59–79) years/57% (223/390) male] with their HbA1c similar to primary care patients [54 (46–61) years], 5.7 (5.3–6.0)%/39 (34–42) mmol/mol (n = 148) vs 5.7 (5.4–6.1)%/39 (36–43) mmol/mol, p = 0.35, but lower than those diagnosed on admission, 10.2 (7.4–13.3)%/88 (57–122) mmol/mol, p &lt; 0.001. Their fasting plasma glucose (FPG) was similar to primary care patients, 5.2 (4.8–5.7) vs 5.2 (4.8–5.9) mmol/L, p = 0.65, but 2hPG higher, 9.0 (7.3–11.4) vs 5.5 (4.4–7.5), p &lt; 0.001.HbA1c identified diabetes in 10% (15/148) with 14 confirmed on OGTT but overall 32% (48/148) were in diabetic range on OGTT. The specificity of HbA1c in 2061 admissions was similar to primary care, 99% vs 96%, p = 0.20, but sensitivity lower, 38% vs 93%, p &lt; 0.001 (63% on FPG/23% on 2hPG, p = 0.037, in those with possible symptoms/complications).Conclusion: HbA1c can play a diagnostic role in acute medicine as it diagnosed another 2% of admissions with diabetes but the discrepancy in sensitivity shows that it does not reflect transient/acute hyperglycaemia resulting from the acute medical event.</p

Comparison of the effects of three insulinotropic drugs on plasma insulin levels after a standard meal

WSTĘP. Porównanie działania repaglinidu, glipizydu i glibenklamidu na wydzielanie insuliny i glukozy po posiłku próbnym zawierającym 500 kcal. MATERIAŁ I METODY. Do krzyżowej, randomizowanej, podwójnie ślepej próby zakwalifikowano 12 pacjentów z wczesną cukrzycą typu 2 (średnia wartość HbA1c 6,1%) oraz 12 osób jako grupę kontrolną. Chorzy losowo otrzymali placebo, 2 mg repaglinidu, 5 mg glipizydu i 5 mg glibenklamidu. Leki podawano po wzorcowym posiłku próbnym, zawierającym 500 kcal. Badania kolejnych leków wykonywano po okresie wydalania poprzedniego z organizmu (7&#8211;12 dni). WYNIKI. Wszystkie trzy leki miały jednakowy wpływ na całkowite posiłkowe wydzielanie insuliny (pole pod krzywą [AUC, area under the curve] -15-240 min). Zauważono jednak wyraźne różnice we wczesnym wydzielaniu insuliny (AUC -15-30 min): u badanych bez cukrzycy zarówno repaglinid, jak i glipizyd zwiększały wydzielanie insuliny odpowiednio o około 61 i 34% w porównaniu z placebo. Wśród chorych na cukrzycę różnica ta wynosiła odpowiednio 37 i 47%. W obu grupach stwierdzono istotną różnicę między glipizydem a glibenklamidem, natomiast repaglinid był skuteczniejszy niż glibenklamid tylko wśród zdrowych pacjentów bez cukrzycy. Wszystkie leki skutecznie obniżały całkowite stężenie glukozy AUC u chorych na cukrzycę i bez niej. Jednak wśród badanych bez cukrzycy repaglinid okazał się znamiennie skuteczniejszy niż glibenklamid. Różnicy takiej nie stwierdzono u chorych na cukrzycę, prawdopodobnie ze względu na częstsze występowanie insulinooporności w tej grupie. WNIOSKI. Repaglinid i glipizyd, ale nie glibenklamid, znacząco poprawiły wczesne wydzielanie insuliny po standardowym posiłku, zarówno wśród badanych bez cukrzycy, jak i wśród chorych na cukrzycę z zachowaną funkcją komórek b trzustki.INTRODUCTION. To compare the effects of repaglinide, glipizide, and glibenclamide on insulin secretion and postprandial glucose after a single standard 500-kcal test meal. MATERIAL AND METHODS. A total of 12 type 2 diabetic patients with early diabetes (mean HbA1c of 6.1%) and 12 matched control subjects were enrolled in this randomized, double-blind, crossover trial. Subjects received placebo, 2 mg repaglinide, 5 mg glipizide, and 5 mg glibenclamide in a random fashion during the trial. Administration of each drug was followed by a single standard 500-kcal test meal. A washout period of 7&#8211;12 days existed between the four study visits. RESULTS. All three drugs were equally effective on the total prandial insulin secretion (area under the curve [AUC] &#8211;15 to 240 min). However, clear differences were noted in the early insulin secretion (AUC &#8211;15 to 30 min); both repaglinide and glipizide increased secretion in nondiabetic subjects by ~61 and 34%, respectively, compared with placebo. In the diabetic patients, the difference versus placebo was 37 and 47%, respectively. The difference between glipizide and glibenclamide reached significance in both groups of subjects, whereas repaglinide was more effective than glibenclamide only in the healthy nondiabetic subject group. All three drugs were effective in decreasing total glucose AUC in the nondiabetic and diabetic population. In the nondiabetic subjects, however, repaglinide was significantly more effective than glibenclamide. The differences disappeared in the diabetic subjects, probably as a result of increased prevalence of insulin resistance in this group. CONCLUSIONS. Repaglinide and glipizide but not glibenclamide significantly enhanced the early insulin secretion in both nondiabetic and diabetic subjects with preserved b-cell function after a single standard meal

Prevalence of admission plasma glucose in 'diabetes' or 'at risk' ranges in hospital emergencies with no prior diagnosis of diabetes by gender, age and ethnicity

Aims To establish the prevalence of admission plasma glucose in 'diabetes' and 'at risk' ranges in emergency hospital admissions with no prior diagnosis of diabetes; characteristics of people with hyperglycaemia; and factors influencing glucose measurement. Methods Electronic patient records for 113 097 hospital admissions over 1 year from 2014 to 2015 included 43 201 emergencies with glucose available for 31 927 (74%) admissions, comprising 22 045 people. Data are presented for 18 965 people with no prior diagnosis of diabetes and glucose available on first attendance. Results Three quarters (14 214) were White Europeans aged 62 (43-78) years, median (IQ range); 12% (2241) South Asians 46 (32-64) years; 9% (1726) Unknown/Other ethnicities 43 (29-61) years; and 4% (784) Afro-Caribbeans 49 (33-63) years,  24 hours. Conclusions Hyperglycaemia was evident in 21% of adults admitted as an emergency; various aspects related to follow-up and initial testing, age and ethnicity need to be considered by professional bodies addressing undiagnosed diabetes in hospital admissions

Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis

Aim: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). Results: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). Conclusion: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis

Comparison of IFCC-calibrated HbA1c from laboratory and point of care testing systems

Objective: WHO, IDF and ADA recommend HbA1c ≥6.5% (48 mmol/mol) for diagnosis of diabetes with pre-diabetes 6.0% (42 mmol/mol) [WHO] or 5.7% (39 mmol/mol) [ADA] to 6.4% (47 mmol/mol). We have compared HbA1c from several methods for research relating glycaemic markers.Research design and methods: HbA1c was measured in EDTA blood from 128 patients with diabetes on IE HPLC analysers (Bio-Rad Variant II NU, Menarini HA8160 and Tosoh G8), point of care systems, POCT, (A1cNow+ disposable cartridges and DCA 2000®+ analyser), affinity chromatography (Primus Ultra2) and the IFCC secondary reference method (Menarini HA8160 calibrated using IFCC SRM protocol).Results: median (IQ range) on IFCC SRM was 7.5% (6.8–8.4) (58(51–68) mmol/mol) HbA1c with minimum 5.3%(34 mmol/mol)/maximum 11.9%(107 mmol/mol). There were positive offsets between IFCC SRM and Bio-Rad Variant II NU, mean difference (1SD), +0.33%(0.17) (+3.6(1.9) mmol/mol), r2 = 0.984, p &lt; 0.001 and Tosoh G8, +0.22%(0.20) (2.4(2.2) mmol/mol), r2 = 0.976, p &lt; 0.001 with a very small negative difference −0.04%(0.11) (−0.4(1.2) mmol/mol), r2 = 0.992, p &lt; 0.001 for Menarini HA8160. POCT methods were less precise with negative offsets for DCA 2000®+ analyser −0.13%(0.28) (−1.4(3.1) mmol/mol), r2 = 0.955, p &lt; 0.001 and A1cNow+ cartridges −0.70%(0.67) (−7.7(7.3) mmol/mol), r2 = 0.699, p &lt; 0.001 (n = 113). Positive biases for Tosoh and Bio-Rad (compared with IFCC SRM) have been eliminated by subsequent revision of calibration.Conclusions: small differences observed between IFCC-calibrated and NGSP certified methods across a wide HbA1c range were confirmed by quality control and external quality assurance. As these offsets affect estimates of diabetes prevalence, the analyser (and calibrator) employed should be considered when evaluating diagnostic data.</p

Metformin Reduces Arterial Stiffness and Improves Endothelial Function in Young Women with Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled, Crossover Trial

Context: Patients with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance and display subclinical evidence of early cardiovascular disease. Metformin improves insulin sensitivity and circulating markers of cardiovascular risk in patients with PCOS, but it is unclear whether this translates into improvements in vascular function. Objective: Our objective was to evaluate the effects of metformin on arterial stiffness and endothelial function in women with PCOS. Design and Intervention: Thirty women with PCOS were assigned to consecutive 12-wk treatment periods of metformin or placebo in a randomized, double-blind, crossover design separated by an 8-wk washout. Main Outcome Measures: The primary outcome measures were assessments of arterial stiffness [augmentation index (AIx), central blood pressure, and brachial and aortic pulse wave velocity (PWV)] and endothelial function. Anthropometry, testosterone, and metabolic biochemistry (lipids, homeostasis model of assessment for insulin resistance, high-sensitivity C-reactive protein, adiponectin, and plasminogen activator inhibitor-1) were also assessed. Results: Metformin improved AIx [−6.1%; 95% confidence interval (CI) for the difference −8.5 to −3.5%; P < 0.001], aortic PWV (−0.76 m/sec; 95% CI for the difference −1.12 to −0.4 m/sec; P < 0.001), brachial PWV (−0.73 m/sec; 95% CI for the difference −1.09 to −0.38; P < 0.001), central blood pressure (P < 0.001), and endothelium-dependent (AIx after albuterol; P = 0.003) and endothelium-independent (AIx after nitroglycerin; P < 0.001) vascular responses. Metformin also reduced weight (P < 0.001), waist circumference (P < 0.001), and triglycerides (P = 0.004) and increased adiponectin (P = 0.001) but did not affect testosterone or other metabolic measures. Conclusions: Short-term metformin therapy improves arterial stiffness and endothelial function in young women with PCOS

Impact of single and multiple sets of resistance exercise in type 1 diabetes

To examine glycemic and glucoregulatory responses to resistance exercise (RE) sessions of different volume in type 1 diabetes (T1DM). Eight T1DM (seven males: one female; age: 38±6 years, HbA1C: 8.7±1.0%/71±11mmol/mol) attended the research facility fasted and on four separate occasions, having taken their usual basal insulin, but omitted morning rapid-acting insulin. Participants completed a 1SET (14min), 2SET (28min), 3SET (42min) RE session (eight exercises×10 repetitions) at 67±3% one-repetition-maximum followed by 60-min recovery, or a resting trial (CON). Venous blood samples were taken before and after exercise. Data (mean±SEM) were analyzed using repeated-measures analysis of variance (P≤0.05). RE did not induce hypoglycemia (BG0.05) with pre-exercise after 3SET. BGIAUC(area-under-curve) (mmol/L/60min) was greater after 1SET and 2SET vs CON (1SET 103.6±36.9 and 2SET 128.7±26.1 vs CON -24.3±15.2, P0.05). Under all trials, plasma creatine kinase levels at 24h post-exercise were similar (P>0.05) to pre-exercise. RE does not induce acute hypoglycemia or damage muscle. BG progressively rose after one and two sets of RE. However, inclusion of a third set attenuated exercise-induced hyperglycemia and returned BG to that of a non-exercise trial