Long-term Glycemic Control Research Articles

The Relationship Between Long-Term Glycemic Control and Partial Remission in Type 1 Diabetes: A Retrospective Study

Aim: Partial remission (PR) is a significant period in the early course of type 1 diabetes (T1D) with implications for diabetes management. We aimed to investigate whether long-term hemoglobin A1c (HbA1c) outcomes in T1D differed as a result of experiencing PR. We also analyzed the demographic and clinical factors that may influence long-term glycemic control.
 Material and methods: We retrospectively tracked the HbA1c values of 131 children and adolescents with T1D over a 5-year period. Patients were stratified into low (

Relation Between HbA1c and Lipid Profile Among Prediabetics, Diabetics, and Non-diabetics: A Hospital-Based Cross-Sectional Analysis.

An unusually high blood glucose level is a hallmark of diabetes mellitus, with an imbalance between insulin levels and insulin sensitivity leading to an insulin functional deficit. Since it serves as both a risk indicator and a gauge of long-term glycemic control, the HbA1c concentration is a crucial component of standard diabetes treatment. The use of the HbA1c concentration in the diagnosis of diabetes is expanding as the test's accuracy increases. Dyslipidemic profiles can appear before type 2 diabetes manifests itself and are independent risk factors for the disease. Additionally, dyslipidemia, especially in diabetics, might affect pancreatic beta-cell survival and activity. This study was undertaken with the aim to find out any correlation between HbA1c and lipid profile among diabetics, prediabetics, and non-diabetics. A total of 1,000 individuals with age 18-60 years were included in the study (non-diabetics = 186, prediabetics = 238, diabetics = 576). HbA1c was estimated by capillary electrophoresis and a lipid profile was done using a fully automatic chemistry analyzer. Diabetes was found to be significantly associated with dyslipidemia. In diabetics, a statistically significant increase in the level of triglyceride and very low-density lipoprotein (VLDL) was seen as compared to prediabetics. Diabetic women were found to be significantly more dyslipidemic as compared to diabetic males. The mean HbA1c among diabetics was found to be 8.3. In hyperglycemia-induced dyslipidemia, raised triglyceride and VLDL were the most common findings, and combined lipid abnormalities were more commonly seen as compared to a single abnormality in the lipid profile. Patients with poor glycemic control more commonly develop dyslipidemia, which may be a reason for an increased incidence of cardiovascular catastrophes in such patients.

A porcine islet-encapsulation device that enables long-term discordant xenotransplantation in immunocompetent diabetic mice

Islet transplantation is an effective treatment for type 1 diabetes (T1D). However, a shortage of donors and the need for immunosuppressants are major issues. The ideal solution is to develop a source of insulin-secreting cells and an immunoprotective method. No bioartificial pancreas (BAP) devices currently meetall of the functions of long-term glycemic control, islet survival, immunoprotection, discordant xenotransplantation feasibility, and biocompatibility. We developed a device in which porcine islets were encapsulated in a highly stable and permeable hydrogel and a biocompatible immunoisolation membrane. Discordant xenotransplantation of the device into diabetic mice improved glycemic control for more than 200days. Glycemic control was also improved in new diabetic mice "relay-transplanted" with the device after its retrieval. The easily retrieved devices exhibited almost no adhesion or fibrosis and showed sustained insulin secretion even after the two xenotransplantations. This device has the potential to be a useful BAP for T1D.

Pars plana vitrectomy for tractional diabetic macular edema with or without internal limiting membrane peeling.

The effectiveness of internal limiting membrane (ILM) peeling in the surgical treatment of tractional diabetic macular edema (DME), although widely examined, remains controversial. This study aimed to assess the efficacy of pars plana vitrectomy (PPV) in the management of tractional DME and to highlight any benefits of additional ILM peeling. This was an open-label, prospective, comparative, and interventional study that enrolled 50 eyes with tractional DME that underwent PPV and allocated each to one of two groups: group A consisted of 25 eyes that had no ILM peeling and group B consisted of 25 eyes that underwent ILM peeling. Postoperative assessments of best-corrected distance visual acuity (BCDVA) in the logarithm of minimal angle of resolution (logMAR) notation and central macular thickness (CMT) were performed at 1, 3, and 6 months postoperatively. At baseline, the two groups were comparable in terms of sex ratios, phakic status, insulin use, coexistence of hypertension, and mean (standard deviation [SD]) age, BCDVA, CMT, duration of diabetes mellitus, and glycosylated hemoglobin (HbA1c) levels. In group A, the mean (SD) BCDVA improved significantly from 0.89 (0.12) logMAR preoperatively to 0.64 (0.24) logMAR (P < 0.001), and the mean (SD) CMT declined significantly from 471.28 (80.83) µm to 228.20 (26.45) µm (P < 0.001), at the 6-month postoperative assessment. Likewise, in group B, the mean (SD) BCDVA improved significantly from 0.83 (0.10) logMAR preoperatively to 0.58 (0.24) logMAR (P < 0.001), and the mean (SD) CMT decreased significantly from 496.84 (89.82) µm to 226.20 (18.04) µm (P < 0.001), after 6 months. There were no significant differences between groups A and B in the changes in BCDVA (Delta BCDVA) or CMT (Delta CMT) at 1, 3, and 6 months postoperatively with respect to the baseline values (all P > 0.05). Postoperative complications were comparable between the two groups. A significant negative correlation was detected between the preoperative HbA1c level and BCDVA improvement in all participants (r = - 0.82; P < 0.001). PPV is an effective treatment for tractional DME. Additional ILM peeling was not significantly associated with functional and anatomical benefits over a short period. Long-term glycemic control plays a role in vision gain after vitrectomy in patients with diabetes. Further long-term studies are required to verify our findings.

Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Long-term HbA1c in 7,961 Children and Young Adults in the Australasian Diabetes Data Network.

The relationship between diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes and long-term glycemic control varies between studies. We aimed, firstly, to characterize the association of DKA and its severity with long-term HbA1c in a large contemporary cohort, and secondly, to identify other independent determinants of long-term HbA1c. Participants were 7,961 children and young adults diagnosed with type 1 diabetes by age 30 years from 2000 to 2019 and followed prospectively in the Australasian Diabetes Data Network (ADDN) until 31 December 2020. Linear mixed-effect models related variables to HbA1c. DKA at diagnosis was present in 2,647 participants (33.2%). Over a median 5.6 (interquartile range 3.2, 9.4) years of follow-up, participants with severe, but not moderate or mild, DKA at diagnosis had a higher mean HbA1c (+0.23%, 95% CI 0.11,0.28; [+2.5 mmol/mol, 95% CI 1.4,3.6]; P < 0.001) compared with those without DKA. Use of continuous subcutaneous insulin infusion (CSII) was independently associated with a lower HbA1c (-0.28%, 95% CI -0.31, -0.25; [-3.1 mmol/mol, 95% CI -3.4, -2.8]; P < 0.001) than multiple daily injections, and CSII use interacted with severe DKA to lower predicted HbA1c. Indigenous status was associated with higher HbA1c (+1.37%, 95% CI 1.15, 1.59; [+15.0 mmol/mol, 95% CI 12.6, 17.4]; P < 0.001), as was residing in postcodes of lower socioeconomic status (most vs. least disadvantaged quintile +0.43%, 95% CI 0.34, 0.52; [+4.7 mmol/mol, 95% CI 3.4, 5.6]; P < 0.001). Severe, but not mild or moderate, DKA at diagnosis was associated with a marginally higher HbA1c over time, an effect that was modified by use of CSII. Indigenous status and lower socioeconomic status were independently associated with higher long-term HbA1c.

Assessment of Glycaemic Control among Diabetic Patients Attending Care at Bowen University Teaching Hospital, Ogbomoso

Background: Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycaemia resulting from impairment in insulin secretion, insulin action or both. The aim of management of diabetes mellitus is to achieve and maintain blood glucose levels within normal ranges and prevent its complications. This study aims to assess the glycaemic control among adult outpatients with diabetes mellitus in Bowen University Teaching Hospital (BUTH), Ogbomoso with a view to intensify effort towards achieving good glycaemic control.&#x0D; Methods: A descriptive cross-sectional study in which 299 consenting diabetic patients were recruited using systematic sampling technique. Sociodemographic characteristics of each participant and their medical history were obtained using a structured interviewer administered questionnaire. The level of glycaemic control was assessed with glycosylated haemoglobin level and recorded for each participant and it was classified as either poor or good. The data collected was analysed using SPSS version 20 software and presented as Descriptive statistics. The association between two or more categorical variable was tested using Chi-square test and fisher’s exact test. Statistical significance was set at p-value less than 0.05.&#x0D; Results: The age group above 60 years had the highest proportion (41.8%) of participants, 60.9% of the participants were females. Majority of the participants (91.6%) were married. About 67.9% of the respondents were in social class 2 and majority of the participants (69.6%) were urban dwellers. Participants on oral anti-diabetic drugs were 62.2% and of this proportion, about 34.1% were on both oral drugs and insulin. About 67.2% of the participants had a duration of diabetes less than 5 years. Most of the participants had a poor glycaemic control with a frequency of 83.6%. The mean level of glycosylated haemoglobin (HbA1C) in this study was 9.2 ± 2.5%. A significant association with glycaemic control was found with the participants age group, sex, level of education and duration on treatment.&#x0D; Conclusion: The long-term glycaemic control of the participants was unacceptably poor. There is need to intensify efforts targeting good glycaemic control in the patients with diabetes mellitus in order to prevent complications from the disease. There is also a need to do further studies to find out the factors associated with poor glycaemic control found in this study.

Glycosylated Hemoglobin (HbA1c) as a Marker for Dyslipidemia in Type 2 Diabetes Mellitus

Objective: The purpose of this research was to examine the effectiveness of HbA1c as a predictor of dyslipidemia in patients with Type-2 Diabetes Mellitus. Study Design: Cross-sectional Place and Duration: Department of Pathology; Women Medical &amp; Dental College Abbottabad in collaboration with Jinnah International Hospital, Abbottabad; April 2022 – September 2022 Methods: After obtaining their agreement, a total of 110 people with Type-2 diabetes mellitus were included in the research. Statistics and background information were recorded. Fasting lipid profile (cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and cholesterol/HDL), HbA1c, creatinine, and electrocardiogram were conducted as part of the comprehensive systemic examination to detect the presence of complications or co-morbidities. Mean, frequency, and correlation analyses are performed in SPSS 22.0. When doing a correlation analysis, the Pearson Chi-square test was typically utilized. Results: Twenty-two patients (20%) had an HbA1c below 7%, whereas eighty-eight patients (80%) had a HbA1c beyond 7%. Dyslipidemia was seen in 62 individuals (56.4%). Direct connections were found between HbA1c and BMI, cholesterol, triglycerides, and low-density lipoprotein (LDL), while an inverse correlation was found between HbA1c and high-density lipoprotein (HDL). When comparing female and male patients, females were shown to have considerably greater TG levels. HbA1c levels were also significantly correlated with the presence of metabolic syndrome, particularly among women (P0.003). Conclusion: According to the findings of our research, HbA1c is not only useful as a biomarker of long-term glycaemic control, but it is also an excellent predictor of lipid profile. Keywords: Lipid Profile, Dyslipidemia, Type 2 Diabetes mellitus, HbA1c

Beneficial effects of adding magnesium to desalinated drinking water on metabolic and insulin resistance parameters among patients with type 2 diabetes mellitus: a randomized controlled clinical trial

There is evidence that increasing the consumption of water containing magnesium can improve glucose metabolism and insulin resistance in patients with type 2 diabetes mellitus (T2DM). This trial was undertaken with the objective of evaluating the effect of adding different concentrations of magnesium chloride to the desalinated drinking water on the glycemic, metabolic, and insulin resistance parameters among patients with T2DM. A randomized cross-sectional controlled clinical trial was conducted to evaluate the effects of adding magnesium chloride supplement to desalinated drinking water consumed by patients with T2DM on the glycemic and metabolic parameters and indicators of insulin sensitivity. The total number of patients with T2DM who successfully completed the trial is 102. Patients were randomly allocated into three groups: the first group received bottled water without added magnesium (0 mg/L) (Group A, n = 37); the second group received bottled water with a low level of magnesium (20 mg/L) (Group B, n = 33); and the third group received drinking water with a high level of magnesium (50 mg/L) (Group C, n = 32). The daily consumption of elemental magnesium for a period of 3 months resulted in significant improvement in HbA1C (8.0 vs 8.2%, p = 0.04), insulin level (7.5 vs 9.9 μIU/mL, p = 0.03), and homeostasis model assessment-estimated insulin resistance (HOMA.IR) (2.5 vs 2.9, p = 0.002) in group C. However, there was no significant improvement in fasting blood glucose (FBS) level or lipid profile. The results of this study suggest that oral magnesium supplementation at the given dose of 50 mg/L daily added to drinking water could improve long-term glycemic control indicators and reduce insulin resistance in patients with T2DM.

Long-term effectiveness of advanced hybrid closed loop in children and adolescents with type 1 diabetes.

Advanced hybrid closed loop (AHCL) systems are the newest tool to improve metabolic control in type 1 diabetes (T1D). Long-term glycemic control of children and adolescents with T1D switching to MiniMed™ 780G in a real clinical setting was evaluated. Time in range (TIR) and in different glucose ranges, glycemic variability indexes, HbA1c and basal-bolus insulin distribution were evaluated in 44 subjects (mean age 14.2 ± 4.0 years, 22 males) during manual mode period, first 14 days (A14d) and first month after auto-mode activation (A1M), first 14 days after 3 months (A3M) and 6 months (A6M) in auto-mode. Mean TIR at A14d was 76.3 ± 9.6% versus 69.3 ± 12.6% in manual mode (p < 0.001), and this improvement was maintained over 6 months. Subjects with TIR >70% and >80% in manual mode were 45% and 23%, respectively, and increased to 80% (p=0.041) and 41% (p=0.007) at A14d. Basal-bolus distribution changed in favor of bolus, and auto-correction boluses inversely correlated with TIR. HbA1c was 7.2 ± 0.7% (55 mmol/mol) at baseline and significantly improved after 3 months (6.7 ± 0.5%, 50 mmol/mol, p < 0.001) and 6 months (6.6 ± 0.5%, 49 mmol/mol, p < 0.001). TIR was higher in individuals >13 years at all time periods (p < 0.001). Glycemic target <120 mg/dl was associated with better TIR. AHCL MiniMed™ 780G allowed rapid and sustained improvement of glycemic control in young T1D patients, reaching recommended TIR. Teenagers showed good technology adherence with optimal TIR, maintained better over time compared to younger children. Stricter settings were associated with better metabolic control, without increase in severe hypoglycemia occurrence.

ODP127 Trabecular Bone Score and Advanced Glycation End Products In Adults with Type 1 Diabetes

Abstract Background Individuals with type 1 diabetes (T1D) have a two- to threefold increase in fracture risk at any site, and up to a sevenfold increase in hip fracture risk compared to those without diabetes. Reduced bone quality appears to contribute to the increased fracture risk observed in this population. Advanced glycation end products (AGEs) tissue accumulation, which reflects long-term glycemic control, may influence bone quality in T1D. Objective We aimed to determine if skin AGEs, as a surrogate marker for bone AGEs, are associated with vertebral trabecular bone score (TBS),anindex of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images and evaluating bone quality. Methods We present preliminary data from subjects with T1D who participated in a cross-sectional study aiming at comparing the prevalence of vertebral fractures between adult subjects with T1D from two tertiary care centers and age-, sex- and BMI-matched controls without diabetes. TBS and bone mineral density (BMD) were assessed using DXA. Skin AGEs were measured by skin autofluorescence. Simple and multiple linear regression analyses were used to explore the factors associated with TBS. Results One hundred and six subjects with T1D (52.8% women; mean age 42.7±14.7 years; mean BMI 26.9±5.6 kg/m 2; mean diabetes duration 27.6±12.3 years; 48.1% with a microvascular complication; mean HbA 1C in the preceding 3 years 7.5±0.9%; mean skin AGEs 2.15±0.54 units; mean TBS 1.428±0.113) were included. Higher skin AGEs were associated with a lower TBS in simple regression analysis (p=0. 012). In multiple linear regression, older age, male sex, higher BMI, current smoking, higher serum calcium, lower lumbar spine and femoral neck BMD, but not skin AGEs, were significantly associated with a lower TBS (model adjusted R 2 =0.65). Conclusion In this population with relatively well-controlled T1D, skin AGEs were not independently associated with TBS. Presentation: No date and time listed

Effects of glucose-lowering agents on cardiovascular and renal outcomes in subjects with type 2 diabetes: An updated meta-analysis of randomized controlled trials with external adjudication of events.

To investigate the effects of glucose-lowering agents on all-cause mortality, and cardiovascular and renal outcomes in adults with type 2 diabetes. A MEDLINE and EMBASE search was performed to identify randomized controlled trials, published up to 28 February 2022, with a follow-up ≥52 weeks, in which glucose-lowering drugs were compared with either placebo or active comparators. We included only trials reporting formal external adjudication of events. All-cause mortality, 3-point MACE (major cardiovascular events), and hospitalization for heart failure (HHF) were considered as principal outcomes. Doubling of serum creatinine, worsening albuminuria, and renal death were considered as secondary endpoints. We included randomized controlled trials performed on metformin (n=17), pioglitazone (n=20), alpha-glucosidase inhibitors (n=9), insulin secretagogues (n=42), dipeptidyl-peptidase-4 inhibitors (n=67), glucagon-like peptide-1 receptor agonists (n=45) or sodium-glucose co-transporter-2 inhibitors (SGLT-2i; n=42) and insulin (n=18). Glucagon-like peptide-1 receptor agonist and SGLT-2i were associated with a significant reduction in all-cause mortality [Mantel-Haenszel odds ratio (MH-OR), 95% confidence interval: 0.88 (0.83; 0.95) and 0.85 (0.79; 0.91), respectively] and MACE [MH-OR, 95% confidence interval: 0.89 (0.84; 0.94) and 0.90 (0.84; 0.96), respectively]. SGLT-2i was associated with a reduced risk of HHF [MH-OR 0.68 (0.62; 0.75)], worsening albuminuria [MH-OR 0.67 (0.55; 0.80)] and doubling of serum creatinine [MH-OR 0.58 (0.44; 0.79)]. Metformin and pioglitazone were associated with a significantly lower risk of MACE [MH-OR 0.60 (0.47; 0.80) and 0.85 (0.74; 0.97), respectively] and pioglitazone with a higher risk of HHF [MH-OR 1.30 (1.04; 1.62)]. Insulin secretagogues were associated with increased risk of all-cause mortality [MH-OR 1.12 (1.01; 1.24)] and MACE [MH-OR 1.19 (1.02; 1.39)]. The results of this updated meta-analysis need to be considered in the choice of drug treatment for type 2 diabetes mellitus, which cannot be merely based on the effect of glucose-lowering drugs on long-term glycaemic control.

Long-Term Influence of Locus of Control and Quality of Life on Metabolic Profile in Elderly Subjects with Type 2 Diabetes.

Background: The Locus of Control (LOC) is a mental disposition indicating the individuals’ belief that disease-related outcomes are under their own control (Internal), dependent on others (External), or dependent on chance (Chance). Quality of Life (QoL) and LOC may have complex effects on self-care activities and diabetes management in subjects with type 2 diabetes (T2D). The aim of the present study was to evaluate the predictive role of LOC and QoL scores on metabolic control in elderly T2D outpatients, secondly evaluating potential gender differences. Methods: An extensive set of questionnaires was administered to a group of consecutive elderly T2D outpatients on oral glucose-lowering drugs attending a single diabetes center. Personal and clinical variables were analyzed at baseline (between 1 February and 31 March 2015) and after 6 years of follow-up. Results: At baseline, study participants showed an overall good metabolic control. Diabetes Specific Quality of Life (DSQoL) scores indicated an overall good QoL in both genders, with a higher DSQoL satisfaction score in women. Both genders presented higher scores in the LOC-Internal domain, with men reaching higher scores in the LOC-External domain than women. At the 6-years follow-up, subjects with baseline higher LOC-External score presented better metabolic outcome. In the regression analysis, LOC-External score was an independent predictor of good metabolic control maintenance, but this result was only statistically significant in men. Conclusions: LOC scores may influence long-term glycemic control in elderly T2D patients on oral glucose-lowering drugs.

Prevalence and predictors of clinical inertia in patients with type 2 diabetes who were treated with a single oral antidiabetic drug.

Clinical inertia, defined as a failure of healthcare providers to initiate or intensify treatment when indicated, is one of the challenges in achieving glycemic targets in type 2 diabetes patients. Using a Japanese medical database compiled from Diagnostic Procedure Combination hospitals, this retrospective study investigated clinical inertia in type 2 diabetes patients treated with a single oral antidiabetic drug. We analyzed predictors of clinical inertia, measured the time to treatment intensification, and monitored patients' glycemic control and renal function for 2 years. The index date was defined as the first date of hemoglobin A1c ≥7.0% during the 180 (±60) days after the first oral antidiabetic drug was prescribed. Clinical inertia was identified in 35.3% of patients. The median time to treatment intensification from the index date was 75.5 days. The proportion of patients achieving hemoglobin A1c <7.0% within 2 years was 33.8% with clinical inertia, and 47.9% without clinical inertia. Multivariate logistic regression analysis showed that Charlson Comorbidity Index score and an interval between visits of ≥6 weeks significantly increased the risk of developing clinical inertia, and hyperlipidemia and higher hemoglobin A1c at baseline significantly decreased the risk. This study showed that clinical inertia in type 2 diabetes patients treated with a single oral antidiabetic drug might have a lasting effect on long-term glycemic control. Our findings will inform clinicians of the characteristics of patients associated with clinical inertia and the importance of providing appropriate treatment under clinical practice guidelines.

Design of Xenopus GLP-1-Based Long-Acting Dual GLP-1/Y2 Receptor Agonists.

GLP-1 receptor (GLP-1R) and neuropeptide Y2 receptor (Y2R) dual agonists have shown great potential to treat obesity and type 2 diabetes (T2DM). We developed a multitarget strategy to design monomeric agonists based on Xenopus GLP-1 (xGLP-1) and PYY3-36 analogues with dual activation activities on GLP-1R and Y2R. A novel peptide, 6q, was obtained via stepwise structure optimization and in vitro receptor screens. In db/db and diet-induced obesity (DIO) mice, 6q produced greater effects on long-term glycemic control and body weight reduction than GLP-1R and Y2R monoagonist counterparts. Notably, in high-fat diet-induced nonalcoholic steatohepatitis (NASH) mice, 6q treatment significantly reduced hepatic triglyceride and total cholesterol levels and reversed hepatic steatosis compared with GLP-1R monoagonist (liraglutide) treatment. Collectively, these data support the therapeutic potential of our GLP-1R/Y2R dual agonist 6q as a novel antidiabetic, antiobesity, and antisteatotic agent.

Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock.

Circadian rhythms drive our daily behaviors to coincide with the earth's rotation on an approximate 24-h cycle. The circadian clock mechanism present in nearly every cell is responsible for our circadian rhythms and is comprised of a transcriptional-translational feedback loop in mammals. The central clock resides in the hypothalamus responding to external light cues, whereas peripheral clocks receive signals from the central clock and are also sensitive to cues from feeding and activity. Of the peripheral clocks, the skeletal muscle clock is particularly sensitive to exercise which has shown to be an important time-cue with the ability to influence and adjust the muscle clock phase in response to exercise timing. Since the skeletal muscle clock is also involved in the expression of tissue-specific gene expression-including glucoregulatory genes-this might suggest a role for exercise timing as a therapeutic strategy in metabolic diseases, like type 2 diabetes. Notably, those with type 2 diabetes have accompanied disruptions in their skeletal muscle clock mechanism which may also be related to the increased risk of type 2 diabetes seen among shift workers. Therefore, the direct influence of exercise on the skeletal muscle clock might support the use of exercise timing to provide disease-mitigating effects. Here, we highlight the potential use of time-of-day exercise as a chronotherapeutic tool within circadian medicine to improve the metabolic profile of type 2 diabetes and support long-term glycemic control, potentially working through the skeletal muscle clock and circadian physiology.

The Paradoxical Role of Circulating Ketone Bodies in Glycemic Control of Individuals with Type 2 Diabetes: High Risk, High Reward?

Introduction: Fasting plasma ketone bodies (KB) are elevated in individuals with type 2 diabetes (T2D) and could affect glycemic control and disease progression. Prolonged KB exposure may result in adaptive beneficial responses, counteracting glycemic dysregulation. In the current proof-of-concept study in adults with T2D, we hypothesized that fasting plasma KB are cross-sectionally associated with poorer glycemic control but prospectively with better glycemic control. Materials and Methods: Fasting plasma KB were measured via nuclear magnetic resonance spectroscopy in patients with T2D treated in primary care (Zodiac cohort; The Netherlands). We analyzed the associations between KB and HbA1c at baseline using linear regression analyses and HbA1c changes over time using linear mixed models. We adjusted for potential confounders, including risk factors for poor glycemic control. Individuals with T2D participating in the general population-based PREVEND study were used as a replication cohort. Results: We included 271 individuals with T2D with a total of 859 HbA1c measurements during a follow-up period of 3.0 (2.0–3.2) years. At baseline, the total amount of fasting plasma KB was independently and positively associated with HbA1c levels (regression coefficient in the fully adjusted analysis = 0.31; 95% CI 0.06–0.57, per doubling of KB; p = 0.02). In contrast, in the longitudinal analyses, fasting plasma KB were associated with a yearly HbA1c (%) decrease of −0.10 (95% CI −0.19 to −0.00 per doubling baseline KB; p = 0.05). Results were replicated in 387 individuals with T2D from a general population cohort with a total of 1115 glucose measurements during a follow-up period of 7.5 (7.2–8.0) years. A yearly decrease in fasting plasma glucose (mmol/L) of 0.09 was found per doubling of baseline KB. Conclusions: This study is the first to suggest a paradoxical role of circulating KB on glycemic control in T2D: elevated KB are associated with cross-sectionally poorer glycemic control but longitudinally with better long-term glycemic control.

Salivary Metabolomics of Well and Poorly Controlled Type 1 and Type 2 Diabetes.

Objective The concentrations of endogenous metabolites in saliva can be altered based on the systemic condition of the hosts and may, in theory, serve as a reflection of systemic disease progression. Hemoglobin A1C is used clinically to measure long-term average glycemic control. The aim of the study was to demonstrate if there were differences in the salivary metabolic profiles between well and poorly controlled type 1 and type 2 subjects with diabetes. Subjects and Methods. Subjects with type 1 and type 2 diabetes were enrolled (n = 40). The subjects were assigned to phenotypic groups based on their current level of A1C: <7 = well-controlled and >7 = poorly controlled. Demographic data, age, gender, and ethnicity, were used to match the two phenotypic groups. Whole saliva samples were collected and immediately stored at −80°C. Samples were spiked using an isotopically labeled internal standard and analyzed by UPLC-TOF-MS using a Waters SYNAPT G2-Si mass spectrometer. Results Unsupervised principal components analysis (PCA) and orthogonal partial least squares regression discrimination analysis (OPLS-DA) were used to define unique metabolomic profiles associated with well and poorly controlled diabetes based on A1C levels. Conclusion OPLS-DA demonstrates good separation of well and poorly controlled in both type 1 and type 2 diabetes. This provides evidence for developing saliva-based monitoring tools for diabetes.

Effectiveness of Student-Led Interventions on Improving Diabetes Outcomes: A Systematic Review

ABSTRACT Background Diabetes education and treatment is a public health priority. Student-delivered strategies have the potential to offer low-cost, high-quality healthcare services to underserved patients while giving students practice experience. However, the effectiveness of these interventions is unknown. Purpose To document study characteristics and the effectiveness of student-delivered interventions on diabetes health outcomes. Methods Databases searched included Medline, CINAHL Plus, and others. Appropriate keywords/subject headings were used to identify studies meeting inclusion criteria. Two reviewers independently extracted data which were compared, and conflicts resolved by discussion. Results Seven studies met inclusion criteria. Six had statistically significant improvement in outcomes including HbA1c, a long-term glycemic control indicator (n = 4), blood pressure (n = 3), physical activity (n = 1), and exercise stage of change (n = 1). Studies involved medical (n = 3), pharmacy (n = 2), nursing (n = 1), and exercise science (n = 1) students. Studies with improved outcomes tended to have more patient contact. Discussion This review provides evidence that student-led diabetes interventions may be effective at improving outcomes, although studies reviewed are limited by lack of comparison groups and representative samples. Translation to Health Education Practice: Student-delivered diabetes interventions may improve outcomes, especially with adequate patient contact time. Studies of theory- and evidence-based student-led diabetes interventions involving health education/promotion students are warranted.

The association between long-term glycemic control and all-cause mortality is different among older versus younger patients with diabetes mellitus and maintenance hemodialysis treatment

AimsKnowledge about association between glycated hemoglobin (HbA1c) and risk of all-cause mortality in patients with diabetes mellitus on maintenance hemodialysis (HD)-treatment is sparse. The study aims to investigate association between HbA1c and all-cause mortality in patients with diabetes and maintenance HD-treatment, separately for two age groups- above and below 75 years. Methods2487 patients (mean age 66 years, 66 % men) were separated in two age groups: ≤75 years (n = 1810) and > 75 years (n = 677) and followed up between 2008 and 2018. Hazard ratios (HR) and 95 % confidence intervals (CI) for associations between HbA1c and all-cause mortality were calculated using Cox-regression-models. Results1295 (52 %) patients died and 473 (70 %) among the patients above 75 years old. In the multivariate analysis, HbA1c5-6 % was used as reference. In patients ≤ 75 years old, only increased HbA1c > 9.7 %, HR2.03(CI1.43–2.89) was associated with increased risk of all-cause mortality. In patients > 75 years, HbA1c ≤ 5 %, HR1.67(CI1.16–2.40); HbA1c6.9–7.8 %, HR1.41(CI1.03–1.93) and HbA1c8.7–9.7 %, HR1.79 (CI1.08–2.96) were associated with increased risk of all-cause mortality. ConclusionsWe found a J-shaped association between HbA1c and mortality only in diabetic HD-patients > 75 years. This probably indicates that in an old population of diabetic HD-patients, both intensive glucose control and hyperglycemia could be harmful and associated with higher risk of death.

Predictive Value of HbA1c and Metabolic Syndrome for Renal Outcome in Non-Diabetic CKD Stage 1-4 Patients.

Glycated hemoglobin (HbA1c) levels are commonly used to indicate long-term glycemic control. An HbA1c level of 6.5–5.7% is defined as pre-diabetes and is proposed as a criterion for diagnosing metabolic syndrome (MetS). However, HbA1c levels can be affected by chronic kidney disease (CKD). Whether HbA1c is associated with clinical outcomes in nondiabetic CKD patients with or without MetS is still unknown. This study included 1270 nondiabetic CKD stage 1–4 Asian patients, divided by HbA1c and MetS. Through linear regression, HbA1c was positively associated with age, waist circumference, hemoglobin levels, and C-reactive protein and was negatively associated with malnutrition–inflammation. HbA1c levels were 5.5% (0.6%) and 5.7% (0.6%) in non-MetS and MetS, respectively (p < 0.001). In Cox regression, higher-level HbA1c was associated with worse composite renal outcome in MetS patients, but with better renal outcome in non-MetS patients: Hazard ratio (HR) (95% confidence interval [CI]) of HbA1c ≥5.7%, compared with HbA1c <5%, was 2.00 (1.06–3.78) in MetS and 0.25 (0.14–0.45) in non-MetS. An association between HbA1c and all-cause mortality was not found. In conclusion, higher HbA1c levels are associated with worse renal outcomes in nondiabetic CKD stage 1–4 patients modified by the presence of MetS.