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The continual increase in global diabetic statistics portends decreased productivity and life spans, thus making it a disease of concern requiring more effective and safe therapeutic options. While several reports on antidiabetic plants, including Hura crepitans, are available, there is still a dearth of information on the holistic antidiabetic properties of H. crepitans and its associated complications. This study evaluated the antidiabetic potential of methanolic extract of Hura crepitans using in vitro, in vivo, and in silico approaches. The extract revealed a dose-dependent in vitro effect, with a 47.97â¯% and 65.34â¯% decrease in the fasting blood sugar levels of streptozotocin (STZ) induced diabetic rats at 150 and 300â¯mg/kg BW, respectively. Likewise, the extract increased serum and pancreatic insulin levels, and significantly ameliorated neuronal oxidative stress and inflammation by reducing the expression levels of cholinesterase, NF-κB, and COX-2 in the brain of hyperglycemic rats. Serum dyslipidemia, liver, and kidney biomarker indices, and hematological alterations in diabetic rats were also significantly attenuated by the extract. Several constituents, mainly terpenes, were identified in the extract. To further predict the drug-likeness, pharmacokinetics, and binding properties of the compounds, in silico analysis was conducted. Ergosta-2,24-dien-26-oicacid,18-(acetyloxy)-5,6-epoxy-4, 22-dihydroxy-1-oxo-,delta.-lactone-4.beta., displayed the highest docking scores for acetylcholinesterase, butyrylcholinesterases, alpha-amylase, and nuclear factor-kB with values of -12.4, -10.9, -10.3, and -9.4â¯kcal/mol, while ergost-25-ene-6,12-dione,3,5-dihydroxy-, (3.beta.,5.alpha.) topped for cyclooxygenase-2 (-9.0â¯kcal/mol). The top-ranked compounds also presented significant oral drug-likeness, pharmacokinetics, and safety properties. Altogether, our data provide preclinical evidence of the potential of Hura crepitans in ameliorating diabetes and its associated complications.
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OBJECTIVE: The aim of this study was to evaluate the trends in the incidence of diabetic neuropathy (DN) and nondiabetic neuropathy (non-DN) in a hospital-based cohort between 2010 and 2019 in Romania. METHODS: We retrospectively analyzed cases with a primary or secondary discharge International Classification of Diseases, Tenth Revision, diagnosis code of neuropathy reported throughout Romania. RESULTS: A total of 1 725 729 hospitalizations with a diagnosis of neuropathy (DN, 769 324 - 44.6%, and non-DN, 956 405- 55.4%) were identified. Women accounted for more DN cases (40 0 936- 52.1%), and men accounted for more non-DN cases (63 7 968- 61.0%). The incidence rate showed an increasing trend during the index period, by a mean rate of 4.3%/year for non-DN and 1.4%/year for DN. Type 2 diabetes was responsible for the overall increase in the incidence rate of DN, whereas in type 1 diabetes, the incidence rate decreased; in both types of diabetes, diabetic polyneuropathy was predominant, whereas autonomic neuropathy had an incidence rate of 10 to 20 times lower than polyneuropathy. The incidence rates of non-DNs increased mainly due to inflammatory polyneuropathies (+3.8%) and uremic neuropathy (+10.3%). CONCLUSION: Using a nationally representative database of hospital-admitted cases, we found that the incidence rates of DN and non-DN increased from 2010 to 2019. The main contributors were type 2 diabetes, inflammatory polyneuropathy, and uremic neuropathy.
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Background: Cardiovascular diseases (CVD) are the main cause of death in the population with diabetes mellitus. This study purposed to determine clinical laboratory markers that might be correlated with the risk of CVD in individuals with type 2 diabetes mellitus (T2DM). Methods: Using data from the Clinical Center of the University of Debrecen from 2016 to 2020, we assessed cardiovascular risk in 5593 individuals with T2DM over a five-year follow-up period. There were 347 new cases of acute myocardial infarction (AMI) and stroke during the period. Following the stratification of these individuals into two groups according to the diagnosis of these CVDs until 2020, the risk of these CVDs was assessed through the utilization of the Chi-square test and Cox proportional hazards regression. Results: The findings of the Cox proportional hazards regression model showed that the number of HbA1C measurements per year (HR = 0.46, 95% CI 0.31-0.7), decreased levels of estimated glomerular filtration rate (eGFR) (HR = 1.6, 95% CI 1.04-2.47), and elevated triglyceride levels (HR = 1.56, 95% CI 1.06-2.29) were correlated with CVD in patients with T2DM. The area under the curve (AUC) was increased from 0.557 (95% CI 0.531-0.582) to 0.628 (95% CI 0.584-0.671) after the inclusion of the laboratory variables into the model showing improved discrimination for AMI and stroke. Conclusions: These findings indicated that eGFR, triglyceride, and the number of HbA1C per year are correlated with AMI and stroke in patients with T2DM.
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AIMS: To capture the types and content of healthcare encounters following severe hypoglycemia requiring emergency medical services (EMS) and to correlate their features with subsequent risk of severe hypoglycemia. METHODS: A retrospective cohort was obtained by linking data from a multi-state health system and an advanced life support ambulance service. This identified 1977 EMS calls by 1028 adults with diabetes experiencing hypoglycemia between 1/1/2013-12/31/2019. We evaluated the healthcare engagement over the following 7 days to identify rates of discussion of hypoglycemia, change of diabetes medications, glucagon prescribing, and referral for diabetes. RESULTS: Rates of hypoglycemia discussion increased with escalating levels of care, from 11.5 % after EMS calls without emergency department (ED) transport or outpatient clinical encounters to 98 % among hospitalized patients with outpatient follow-up. EMS transport and outpatient follow-up were associated with significantly higher odds of discussion of hypoglycemia (OR 60 and OR 22.1, respectively). Interventions were not impacted by previous severe hypoglycemia within 30 days. Prescription of glucagon was rare among all patients. CONCLUSIONS: Interventions to prevent recurrent hypoglycemia increase with escalating levels of care but remain inadequate and inconsistent with clinical guidelines. Greater attention is needed to ensure timely diabetes-related follow-up and treatment modification for patients experiencing severe hypoglycemia.
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Emergency Medical Services , Hypoglycemia , Humans , Hypoglycemia/epidemiology , Hypoglycemia/therapy , Female , Male , Retrospective Studies , Middle Aged , Emergency Medical Services/statistics & numerical data , Aged , Adult , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus/therapy , Diabetes Mellitus/epidemiology , Diabetes Mellitus/drug therapy , Aftercare/statistics & numerical data , Follow-Up StudiesABSTRACT
Background: The primary aim of this study was to investigate the correlation between diabetic retinopathy (DR) and the HALP score (hemoglobin, albumin, lymphocyte, and platelet) in individuals with diabetes within the United States population. Methods: This cross-sectional investigation was based on the National Health and Nutrition Examination Survey (NHANES) database from 2003-2018. The following module calculated the HALP score: HALP score = [lymphocytes (/L) × hemoglobin (g/L) × albumin (g/L)]/platelets (/L). By performing the receiver operating characteristic (ROC) analysis, the optimal cutoff value of HALP was ascertained. Restricted cubic splines (RCS), multivariable logistic regression analysis, sensitivity analysis, and subgroup analysis were conducted to evaluate the effect of the HALP score on DR patients. Finally, the decision curve analysis (DCA) and clinical impact curve (CIC) were conducted to estimate the predictive power and clinical utility of the HALP score with clinical indicators. Results: According to the cutoff value (42.9) determined by the ROC curve, the participants were stratified into a lower HALP group (HALPlow) and a higher HALP group (HALPhigh). An L-shaped relationship between HALP score and DR risk was presented in the RCS model (P for nonlinearity <0.001). The DR risk sharply decreased with the increase of HALP, and the decline reached a plateau when HALP was more than 42.9. After fully adjustment, the multivariate logistic regression analysis found that HALPlow was an independent risk factor for DR (OR = 1.363, 95% CI: 1.111-1.671, P < 0.001). Besides, sensitivity analysis showed consistent results. Furthermore, the combination of HALP score and clinical indicators demonstrated predictive power and clinical utility, as shown by the ROC curve, DCA, and CIC. Conclusion: The HALP score has an L-shaped correlation with the risk of DR, and thus, the HALP score may contribute to the timely intervention of diabetes patients.
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Blood Platelets , Diabetic Retinopathy , Hemoglobins , Lymphocytes , Nutrition Surveys , Humans , Diabetic Retinopathy/blood , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/diagnosis , Male , Female , Middle Aged , Cross-Sectional Studies , United States/epidemiology , Hemoglobins/analysis , Hemoglobins/metabolism , Blood Platelets/pathology , Adult , Risk Factors , Aged , Serum Albumin/analysis , Serum Albumin/metabolism , ROC Curve , Biomarkers/bloodABSTRACT
AIM: To evaluate whether 1-hour plasma glucose (1hPG) can be a comparable measurement to 2-hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes. METHODS: A total of 1026 non-diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6-, 20- and 30year follow-up for outcomes including diabetes, all-cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a '1hPG-normal' group (1hPG <8.6 mmol/L) and a '1hPG-high' group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time-dependent receiver-operating characteristic (ROC) curve. RESULTS: Compared with the 1hPG-normal group, the 1hPG-high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43-5.79), all-cause mortality (HR 1.46, 95% CI 1.07-2.01), CVD mortality (HR 1.84, 95% CI 1.16-2.95), CVD events (HR 1.39, 95% CI 1.03-1.86) and microvascular disease (HR 1.70, 95% CI: 1.03-2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long-term follow-up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009). CONCLUSIONS: Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long-term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.
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Blood Glucose , Diabetes Mellitus, Type 2 , Predictive Value of Tests , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Male , Female , Middle Aged , Blood Glucose/analysis , Blood Glucose/metabolism , Follow-Up Studies , China/epidemiology , Glucose Tolerance Test , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/blood , Cardiovascular Diseases/mortality , Glucose Intolerance/blood , Glucose Intolerance/diagnosis , Glucose Intolerance/complications , Adult , Diabetes Complications/blood , Diabetes Complications/epidemiology , Aged , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/blood , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/prevention & control , Diabetic Angiopathies/mortality , ROC CurveABSTRACT
The American Society of Anesthesiologists (ASA) Task Force recently recommended discontinuing glucagon-like peptide-1 receptor agonist (GLP-1 RA) agents before surgery because of the potential risk of pulmonary aspiration. However, there is limited scientific evidence to support this recommendation, and holding GLP-1 RA treatment may worsen glycemic control in patients with diabetes. As we await further safety data to manage GLP-1 RA in the perioperative period, we suggest an alternative multidisciplinary approach to manage patients undergoing elective surgery. Well-conducted observational and prospective studies are needed to determine the risk of pulmonary aspiration in persons receiving GLP-1 RA for the treatment of diabetes and obesity, as well as the short-term impact of discontinuing GLP-1 RA on glycemic control before elective procedures in persons with diabetes.
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Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention. Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases. Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons. Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.
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Introduction: Kidney transplantation is associated with an increased risk of posttransplant diabetes mellitus (PTDM), impacting recipient and graft survivals. The incidence of PTDM ranges from 15% to 30%, with most cases occurring in the first year post-transplant. Some clinical and laboratory characteristics pre- and post-transplant may be associated with a higher PTDM incidence in a more extended follow-up period. This study aimed to analyze the prevalence of PTDM among renal transplant recipients without previous DM diagnosis during a five-year post-transplant follow-up, as well as clinical and laboratory characteristics associated with a higher incidence of PTDM during this period. Material and methods: Single-center retrospective cohort including kidney transplant recipients older than 18 years with a functioning graft over six months of follow-up between January and December 2018. Exclusion criteria were recipients younger than 18 years at kidney transplantation, previous diabetes mellitus diagnosis, and death with a functioning graft or graft failure within six months post-transplant. Results: From 117 kidney transplants performed during the period, 71 (60.7%) fulfilled the inclusion criteria, 18 (25.3%) had PTDM diagnosis, and most (n=16, 88.9%) during the 1st year post-transplant. The need for insulin therapy during the hospital stay was significantly higher in the PTDM group (n=11, 61.1% vs. n=14, 26.4%, PTDM vs. non-PTDM). Other PTDM risk factors, such as older age, high body mass index, HLA mismatches, and cytomegalovirus or hepatitis C virus infections, were not associated with PTDM occurrence in this series. During 5-year post-transplant follow-up, the graft function remained stable in both groups. Conclusion: The accumulated incidence of PTDM in this series was similar to the reported in other studies. The perioperative hyperglycemia with the need for treatment with insulin before hospital discharge was associated with PTDM.
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Diabetic muscle infarction (DMI) is a rare yet serious complication that has been strongly associated with uncontrolled diabetes, although other risk factors are unclear. DMI is an uncommon complication of diabetes with a lack of structured guidelines for evaluation or management. End-stage renal disease (ESRD) could have further implications in patients with DMI in terms of management given that nonsteroidal anti-inflammatory drugs (NSAIDs), which have been shown to reduce the recovery times and recurrence of DMI, could be contraindicated. We present a rare case of DMI in an African American man with ESRD who presented for new-onset right lower-extremity pain and swelling. We discuss the challenges involved with the diagnosis and treatment of this rare condition. This case adds to the knowledge of DMI, which is limited because of the low incidence of this condition, and it helps us understand how this condition affects the African American population and patients with ESRD.
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Bilateral hyperglycemic nonketotic chorea is a rare complication of hyperglycemia. In most cases, the literature illustrates patients presenting with unilateral chorea with image findings significant for hyperintense lesions in the basal ganglia on magnetic resonance imaging (MRI) or hyperdensities on computerized tomography (CT). Here, we present a case of an 83-year-old patient who was admitted to the hospital due to acute onset of orofacial and bilateral upper extremity chorea. She had no previous history of infection, genetic mutation, neoplasms, neurodegeneration, stroke, metabolic disease, drug exposure, or autoimmune disease. Surprisingly, her MRI showed only chronic microvascular changes in periventricular white matter without basal ganglia abnormalities. However, she was noted to have marked worsening of her glycemic control over the preceding 12 months based on worsening glycated hemoglobin (HbA1c) levels and elevated serum glucose on presentation. A literature review indicates that chorea caused by hyperglycemia is at times reversible with glycemic control, but as demonstrated in our patient, this is not always necessarily the case. A similar course has only been elaborated in a few other cases in the literature. We will also review the pathogenesis, the usual disease clinical course and standard treatment from the literature.
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Introduction: Diabetes mellitus (DM) and cardiovascular disease (CVD) such as acute myocardial infarction, stroke, and coronary artery disease are highly prevalent conditions that are responsible for significant morbidity and mortality, particularly in Hungary. The conditions are attributed to identical risk factors, and individuals with DM are primarily susceptible to cardiovascular complications, which are the leading causes of death and disability in patients with DM. The objective of this study was to estimate the prevalence of CVD in individuals with DM and to investigate the association between potential risk factors and the presence of CVD among individuals with DM in a population-based sample. Methods: The study was based on data from three waves of the European Health Interview Surveys (EHIS) conducted in Hungary in 2009, 2014, and 2019. Results: The prevalence of CVD among patients with DM decreased during the study period and that socioeconomic factors, cardiometabolic risk factors including high blood pressure and high cholesterol, and depression are major contributors to CVD burden in patients with DM in Hungary. Discussion: Our findings suggest the importance of regular check-up for hypertension and hypercholesterolemia, better focus on socioeconomic status, as well as ongoing monitoring of mental health among patients with diabetes. Further research is needed to understand the potential causes behind the observed decrease in CVD prevalence.
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Cardiovascular Diseases , Diabetes Mellitus , Hypertension , Humans , Adult , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Hungary/epidemiology , Diabetes Mellitus/epidemiology , Risk Factors , Hypertension/complications , Hypertension/epidemiologyABSTRACT
Background: Diabetic foot ulcers (DFUs) are debilitating to the patient and costly for the healthcare system. We set up the Diabetic Rapid Evaluation and lower limb Amputation Management (DREAM) clinic with the aim of providing early directed specialist care to patients with DFUs. With early management, we hope to treat DFUs in its early stages, reducing the need for and associated morbidity of major and minor lower limb amputations. Objectives: We evaluated the outcomes of the fast-access DREAM clinic with multi-disciplinary evaluation for patients with DFUs. Outcomes include time from the point of referral to DREAM clinic evaluation, amputation rates and wound healing rates. Design: Patients presenting with DFU to the DREAM clinic were enrolled. A podiatrist made the first assessment, followed by immediate specialist consultation with Endocrinologists, Vascular surgeons or Orthopaedic surgeons as required. Methods: Data on baseline demographics and DFU characteristics were collected. Outcomes evaluated were wound healing at 12 weeks, wound salvage rates, time to DREAM clinic access and time to specialist referral. Results: Sixty-eight patients were enrolled, with 57.3% males, and mean age of 63 ± 13.0 years. Majority of ulcers were classified as neuropathic (41.3%) and located at the digits (40%). At 12-weeks follow-up, 1 had undergone major amputation, 9 minor amputations and 4 surgical debridements. The median time to DREAM clinic evaluation from first presentation was 3 days (IQR 7). Eleven (16.2%) required >1 specialist consult. Twenty (29.4%) were hospitalised for treatment. Twelve underwent revascularisation within 4 days (IQR 3.5). Twenty-four patients (35.3%) continued podiatry follow-up, having 28 DFUs in which 20 (71.4%) healed within 12 weeks. Conclusion: The fast-access multidisciplinary DREAM clinic shows promising outcomes with lower major amputation rates and exemplary DFU healing outcomes.
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INTRODUCTION: We have developed the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes model, an individual-level, discrete-time microsimulation model specifically designed for type 2 diabetes (T2D) management. This study aims to validate the model's performance when populated exclusively with a fully de-identified dataset to ensure its applicability in secure settings. METHODS: Patient-level data from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial were fully de-identified by removing all identifiable information and masking numerical values (e.g., age, body mass index) within ranges to minimize the risk of re-identification. To populate the simulation, we imputed the masked numerical values using data from the National Health and Nutrition Examination Survey (NHANES). We applied the BRAVO model to the baseline data to predict 7-year study outcomes for the EXSCEL trial and assessed its discrimination power and calibration using C-statistics and Brier scores. RESULTS: The model demonstrated acceptable discrimination and calibration in predicting the first occurrence of non-fatal myocardial infarction, non-fatal stroke, heart failure, revascularization, and all-cause mortality. Even with the fully deidentified data from the EXSCEL trial primarily presented in ranges rather than specific values, the BRAVO model exhibited robust prediction performance for diabetes complications and mortality. CONCLUSIONS: This study demonstrates the feasibility of using the BRAVO model in settings where only fully de-identified patient-level data are available.
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BACKGROUND: The treatment of severe diabetic toe infection complicated with osteomyelitis is often surgical. The decision on the level of amputation, when required, is difficult. Very few articles reported comparative outcomes between toe amputation and ray resection, and only in relation to the hallux. The aim of this preliminary report is to record the results of these procedures when performed on all toes. METHODS: This is a comparative retrospective study where the charts of a continuous series of 44 patients (48 procedures) with diabetic forefoot infection were analyzed. Only cases of severe infection with confirmed osteomyelitis were included. Two groups were compared based on the level of amputation: the toe amputation group (at and distal to the metatarsophalangeal joint) and the ray resection group (distal to tarsometatarsal joint). The primary outcomes were defined as osteomyelitis recurrence and re-amputation. RESULTS: Outcome comparison between toe amputation and ray resection; 47.3 % vs. 51.7 % had a recurrence of their osteomyelitis (p = 0.8), 36.8 % vs. 34.5 % had a re-amputation (p = 0.02). Re-amputation was needed in 25 % of cases following hallux/first ray index procedure while the same was required in 39 % of cases following lateral toes/rays index procedures (p = 0.4). Both primary outcomes were correlated to CDK, smoking and creatinine level. CONCLUSIONS: Bone infection recurrence and re-amputation are highly prevalent in patients undergoing initial amputation for severe diabetic toe infection. A more aggressive approach in the form of a more proximal level of index amputation might be needed when treating severe toe infections with osteomyelitis in patients with diabetes.
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Diabetes Mellitus , Diabetic Foot , Osteomyelitis , Humans , Retrospective Studies , Ulcer/complications , Diabetic Foot/complications , Diabetic Foot/surgery , Toes/surgery , Amputation, Surgical , Osteomyelitis/complications , Osteomyelitis/surgeryABSTRACT
INTRODUCTION: Hypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes. RESEARCH DESIGN AND METHODS: Twenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry. RESULTS: In total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10-3) and isoleucine (p=2.2×10-3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days. CONCLUSIONS: In individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations. TRIAL REGISTRATION NUMBER: NCT01337362.
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Diabetes Mellitus, Type 1 , Hypoglycemia , Hypoglycemic Agents , Humans , Amino Acids , Amino Acids, Branched-Chain , Blood Glucose/analysis , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , Fatty Acids , Hypoglycemia/chemically induced , Hypoglycemic Agents/therapeutic use , Insulin , Isoleucine/blood , Leucine/bloodABSTRACT
AIM: To evaluate the MONA.health artificial intelligence screening software for detecting referable diabetic retinopathy (DR) and diabetic macular edema (DME), including subgroup analysis. METHODS: The algorithm's threshold value was fixed at the 90% sensitivity operating point on the receiver operating curve to perform the disease classification. Diagnostic performance was appraised on a private test set and publicly available datasets. Stratification analysis was executed on the private test set considering age, ethnicity, sex, insulin dependency, year of examination, camera type, image quality, and dilatation status. RESULTS: The software displayed an area under the curve (AUC) of 97.28% for DR and 98.08% for DME on the private test set. The specificity and sensitivity for combined DR and DME predictions were 94.24 and 90.91%, respectively. The AUC ranged from 96.91 to 97.99% on the publicly available datasets for DR. AUC values were above 95% in all subgroups, with lower predictive values found for individuals above the age of 65 (82.51% sensitivity) and Caucasians (84.03% sensitivity). CONCLUSION: We report good overall performance of the MONA.health screening software for DR and DME. The software performance remains stable with no significant deterioration of the deep learning models in any studied strata.
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BACKGROUND: With the rising prevalence of diabetes, machine learning (ML) models have been increasingly used for prediction of diabetes and its complications, due to their ability to handle large complex data sets. This study aims to evaluate the quality and performance of ML models developed to predict microvascular and macrovascular diabetes complications in an adult Type 2 diabetes population. METHODS: A systematic review was conducted in MEDLINE®, Embase®, the Cochrane® Library, Web of Science®, and DBLP Computer Science Bibliography databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. Studies that developed or validated ML prediction models for microvascular or macrovascular complications in people with Type 2 diabetes were included. Prediction performance was evaluated using area under the receiver operating characteristic curve (AUC). An AUC >0.75 indicates clearly useful discrimination performance, while a positive mean relative AUC difference indicates better comparative model performance. RESULTS: Of 13 606 articles screened, 32 studies comprising 87 ML models were included. Neural networks (n = 15) were the most frequently utilized. Age, duration of diabetes, and body mass index were common predictors in ML models. Across predicted outcomes, 36% of the models demonstrated clearly useful discrimination. Most ML models reported positive mean relative AUC compared with non-ML methods, with random forest showing the best overall performance for microvascular and macrovascular outcomes. Majority (n = 31) of studies had high risk of bias. CONCLUSIONS: Random forest was found to have the overall best prediction performance. Current ML prediction models remain largely exploratory, and external validation studies are required before their clinical implementation. PROTOCOL REGISTRATION: Open Science Framework (registration number: 10.17605/OSF.IO/UP49X).
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Diabetes Mellitus, Type 2 , Adult , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Machine Learning , Neural Networks, Computer , ROC CurveABSTRACT
INTRODUCTION: The purpose of this systematic review was to study whether contrast sensitivity assessment in people with diabetes could be a reliable test in early detection of diabetic retinopathy. A systematic search based on population, intervention, comparison, and outcome strategy was performed. METHODS: PubMed, Scopus, and Web of Science were searched for English articles of human patients with type 1 and type 2 diabetes and contrast sensitivity measurements as domain studied. RESULTS: Twentyone comparative cross-sectional studies were included. All of them showed significant loss of contrast sensitivity in people with diabetes and diabetic retinopathy regarding control patients of the same age, regardless of the method used. However, those without diabetic retinopathy, involve a loss of contrast sensitivity, although not always significant. CONCLUSION: Changes in contrast sensitivity suggest that there is damage to the retina prior to the vascular ones and that they could be detected by this test.