Persistent Fasting Hyperglycemia Research Articles

The Other Side of the Perfect Cup: Coffee-Derived Non-Polyphenols and Their Roles in Mitigating Factors Affecting the Pathogenesis of Type 2 Diabetes.

The global prevalence of type 2 diabetes (T2D) is 10.5% among adults in the age range of 20-79 years. The primary marker of T2D is persistent fasting hyperglycemia, resulting from insulin resistance and β-cell dysfunction. Multiple factors can promote the development of T2D, including obesity, inflammation, and oxidative stress. In contrast, dietary choices have been shown to prevent the onset of T2D. Oatmeal, lean proteins, fruits, and non-starchy vegetables have all been reported to decrease the likelihood of T2D onset. One of the most widely consumed beverages in the world, coffee, has also demonstrated an impressive ability to reduce T2D risk. Coffee contains a diverse array of bioactive molecules. The antidiabetic effects of coffee-derived polyphenols have been thoroughly described and recently reviewed; however, several non-polyphenolic molecules are less prominent but still elicit potent physiological actions. This review summarizes the effects of select coffee-derived non-polyphenols on various aspects of T2D pathogenesis.

Can We Predict Isolated Fasting Hyperglycemia in Patients With GDM? [ID: 1368593

INTRODUCTION: One-third of patients with gestational diabetes mellitus (GDM) require hypoglycemic agents. There is a subset of patients who control their postprandial values with diet, yet they have persistent fasting hyperglycemia requiring bedtime hypoglycemic agents (GDMHS). As fasting hyperglycemia is an independent risk factor for adverse pregnancy outcomes, we aimed to identify risk factors to predict (and subsequently counsel) GDM patients with a risk of isolated fasting hyperglycemia requiring treatment with bedtime hypoglycemic agents. METHODS: This was an IRB-approved retrospective cohort study of patients diagnosed with GDM after 24 weeks from 2016 to 2020. Patients monitored glucose four times daily (fasting and 2 hours postprandial); fasting hyperglycemia was defined as more than 50% fasting values greater than 90 mg/dL. Patients completely controlled with diet (GDMA1) were compared to those with GDMHS. A multivariate analysis assessed whether age, body mass index (BMI), fasting glucose tolerance test (GTT) value, HbA1c at diagnosis, history of polycystic ovarian syndrome or previous GDM, Asian race, or family history of diabetes predicted isolated fasting hyperglycemia. RESULTS: Four hundred five patients had GDM. 57% had GDMA1, and 28% had GDMHS. Compared to GDMA1, patients with GDMHS were older, had higher BMI, higher fasting GTT value, higher HbA1c, and higher incidence of previous GDM or family history of diabetes. After adjusting for confounders, higher HbA1c at GDM diagnosis (odds ratio [OR] 3.55), older age (OR 1.08), and higher fasting GTT value (OR 1.06) were significantly associated with an increased probability of persistent fasting hyperglycemia. Asian race was associated with decreased probability of fasting hyperglycemia but was confounded by lower fasting GTT and lower BMI. CONCLUSION: Our data suggest that elevated HbA1c, higher fasting GTT value, and older age may predict persistent isolated fasting hyperglycemia in GDM patients who are otherwise controlled with diet. These data can be used to educate and counsel patients to alleviate frustration encountered with persistent fasting hyperglycemia despite postprandial diet control.

Use of the turbidimetric method for determining hemoglobin (A1C) in diabetic and nondiabetic dogs

Canine diabetes mellitus is a multifactorial disease with a worldwide prevalence of 0.005 to 1.5%, affecting dogs between 4 and 14 years of age, males and females. Persistent fasting hyperglycemia and glycosuria confirm the diagnosis, and glycated hemoglobin (A1C) is an efficient biomarker for the risk of complications and monitoring. The scarcity of unvalidated reference values and commercial kits justifies its low application in veterinary medicine. The aim of this study was to identify A1C as a diagnostic biomarker of diabetes mellitus in dogs through immunoturbidimetry assay and to propose an A1C reference range for diabetic and nondiabetic dogs. We randomly selected 86 healthy dogs and 20 diabetic dogs of different ages and breeds, both male and female, neutered and not neutered. Hemogram, urea, creatinine, alanine aminotransferase, alkaline phosphatase, glycemia, and glycated hemoglobin were performed using the turbidimetry assay. The Spearman correlation test between A1C and the biochemical and hematological variables, ROC curve to analyze the diagnostic capacity of glucose, and A1C to predict diabetes in dogs was used. We obtained a median of 3.8% for A1C with a confidence interval of 3.8 to 4.0% for nondiabetic dogs and a cut off of 4.5% for diabetic dogs. Spearman’s correlation showed a direct relationship between A1C and glucose and a statistically significant association with glucose (p < 0.001) and creatinine (p < 0.002). The areas of the ROC curve of A1C and glucose had good indices in their individual use, and their association showed a positive and statistically significant correlation (p = 0.051). The diagnostic ability of A1C to predict diabetes mellitus in dogs was confirmed and A1C reference range established for nondiabetic and diabetic dogs, also showing association with creatinine, given this relevant and unprecedented data in the veterinary literature.

Serum Fructosamine Concentration in Uncontrolled Hyperthyroid Diabetic Cats Is within the Population Reference Interval.

Diabetes mellitus is a common endocrinopathy of cats that is characterized by persistent fasting hyperglycemia. However, stress induces substantial hyperglycemia in cats that poses a challenge to the veterinarian who may wrongly interpret the high serum concentration of blood glucose as evidence of diabetes mellitus. Fructosamine is a glycated serum protein that serves as an index of glycemic control in cats and is useful because it is not affected by stress hyperglycemia. However, factors such as body weight, hypoproteinemia, and increased serum thyroid hormone concentration can alter fructosamine concentration. The goal of this retrospective study was to compare the fructosamine concentrations in diabetic and nondiabetic cats with and without uncontrolled hyperthyroidism. A secondary goal was to determine the effect of sex, age, different populations of cats, and diabetes on the variability of fructosamine. We found that the mean (±SE) serum fructosamine of hyperthyroid diabetic cats (332 ± 24 µmol/L, 95% CI 291–379 µmol/L) was within the population-based reference interval (200–360 µmol/L) and significantly lower in comparison to euthyroid diabetic cats (527 ± 10 µmol/L, 95% CI 515–553 µmol/L). Additionally, in this study, diabetes accounted only for approximately 50% of the variance in serum fructosamine, while age, sex, and population made a minor contribution to this variance. In conclusion, finding serum fructosamine that is within the population-based reference interval in an uncontrolled diabetic cat should alert the veterinarian to the possibility of concurrent hyperthyroidism. Additionally, the veterinary clinician should consider that serum fructosamine might be substantially affected by factors other than diabetes.

Concordance of two diabetes diagnostic criteria using fasting plasma glucose and hemoglobin A1c: the Yuport Medical Checkup Centre study.

BackgroundWe tested the concordance of the two diagnostic criteria for diabetes using fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) by the Japan Diabetes Society (JDS) and American Diabetes Association (ADA).MethodsWe used data from 7,328 subjects without known diabetes who participated in a voluntary health checkup program at least twice between 1998 and 2006, at intervals ≤2 years. For repeat participants who attended the screening over two times, data from the first and second checkups were used for this study. At the first visit, diabetes was diagnosed both at FPG ≥7.0 mmol/L and HbA1c ≥6.5% using the JDS criteria. In addition, diabetes was diagnosed using two ADA criteria; ADA-FPG diabetes for persistent fasting hyperglycemia (FPG ≥7.0 mmol/L) or ADA-HbA1c diabetes for hyper-glycated hemoglominemia (HbA1c ≥6.5%), both at the first and second checkups. Subsequently, the concordance of diagnosis between the JDS and the ADA criteria was evaluated.ResultsAt the first checkup, 153 (2.1%) persons were diagnosed with diabetes by the JDS criteria. They had higher levels of risk factors for diabetes than non-diabetic subjects. Using the first and second checkups, 174 (2.4%) and 175 (2.4%) were diagnosed with diabetes by the ADA-FPG criteria, respectively. Among 153 subjects diagnosed with diabetes by the JDS criteria, 125 (81.7%) and 129 (84.3%) had ADA-FPG and ADA-HbA1c diabetes, respectively. The kappa coefficients of the JDS criteria with ADA-FPG and ADA-HbA1c criteria were 0.759 and 0.782 (P<0.001), respectively. In the subgroup analysis stratified by sex, the concordance was well preserved at the kappa coefficients around 0.8 (between 0.725 and 0.836).ConclusionThe JDS diagnostic criteria for diabetes have a substantial and acceptable concordance with the ADA criteria. The JDS criteria may be a practical method for diagnosing diabetes that maintains compatibility with the ADA criteria.

Clinicopathologic Characterization of Naturally Occurring Diabetes Mellitus in Vervet Monkeys

Diabetes mellitus (DM) is a group of chronic metabolic diseases characterized by persistent fasting hyperglycemia, and it can be of either polygenic or monogenic origin. Animal models have played an important role in elucidating the pathophysiology of the polygenic Type 1 and type 2 DM forms; however, useful animal models of the monogenic forms do not exist. The authors describe 4 cases of naturally occurring DM in vervet monkeys (Chlorocebus aethiops sabaeus), 1 of which has clinicopathologic findings consistent with type 2 DM, including persistent hyperglycemia, hypertriglyceridemia, islet amyloidosis, and reduced islet insulin immunostaining. In contrast, the 3 remaining animals have clinicopathologic similarities to a monogenic form of the disease, including a lack of islet amyloidosis and hypertriglyceridemia, as well as normal islet insulin immunostaining. In addition, pedigree analysis conducted on one of these animals is consistent with either an autosomal dominant or mitochondrial inheritance pattern, which supports a monogenic form of DM. The authors thus hypothesize that a naturally occurring monogenic form of diabetes may occur in vervet monkeys, making them a potential animal model for future studies.

Latent Autoimmune Diabetes in Adults and Pregnancy: Foretelling the Future

W.S. is a 25-year-old woman referred for newly diagnosed gestational diabetes mellitus (GDM) after having a 1-hour plasma glucose (PG) of 150 mg/dl during a 50-g glucose challenge test at 28 weeks' gestation. She denied any history of polyuria, polydipsia, polyphagia, or visual disturbances. During this pregnancy, she had gained only 5 lb by 31 weeks and denied any complications. Before the pregnancy, her baseline weight was 205 lb, and her BMI 33 kg/m2. Overall, she was feeling well and tolerating her pregnancy well. Her medical history was significant for a single pregnancy 4 years ago that was not complicated by GDM. She delivered a healthy, full-term girl weighing 7 lb, 4 oz, by an uncomplicated spontaneous vaginal delivery (SVD). She denied any subsequent history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). She denied a family history of type 2 diabetes. However, her 4-year-old daughter had been diagnosed with type 1 diabetes. She denied any tobacco or alcohol use. After being diagnosed with GDM, she received appropriate dietary counseling and was instructed in home blood glucose monitoring. Secondary to persistent fasting hyperglycemia, she was started on human insulin NPH, 5 units subcutaneously daily at bedtime. She continued to monitor fasting and 2-hour postprandial blood glucose values. Her GDM was followed closely, and her NPH insulin was titrated to 14 units at bedtime. Because of ongoing postprandial hyperglycemia, insulin lispro was added for prandial coverage, in a dose of 1 unit/20 g of carbohydrate consumed. Her blood glucose control improved on intensive insulin therapy. Her hemoglobin A1c (A1C) was excellent at 5.5%. At term, she delivered a healthy boy of 8 lb, 8 oz, by uncomplicated SVD. The patient was scheduled for a postpartum follow-up, including a 75-g oral glucose tolerance test (OGTT). She denied …

Gestational diabetes: The significance of persistent fasting hyperglycemia for the subsequent development of diabetes mellitus

There are little data regarding the temporal pattern of hyperglycaemia during gestational diabetes (GDM) and its significance for the development of future diabetes. The aim of this study was to examine the relationship between fasting and postprandial hyperglycemia in a GDM pregnancy, with the development of subsequent diabetes mellitus (DM). Participants with a history of GDM were identified by a medical records review and invited to be tested for diabetes. One hundred and two participants participated in the study, up to 8 years after their pregnancy. Diabetes had developed in 29%, and 16% had impaired glucose tolerance. Pregnancy factors predictive for the development of diabetes included BMI, the fasting and 2-h BGL on the GTT, and the use of insulin. We used the need for bedtime intermediate-acting insulin as an indicator of persistent fasting hyperglycemia and the need for prandial short-acting insulin as a marker of postprandial hyperglycemia. Compared with participants not treated with insulin, those requiring bedtime insulin had a relative risk of 6.2 (95% CI=2.7–14.1, P<.001) for the development of diabetes. However, participants who required prandial insulin only did not have a higher likelihood of diabetes, compared with those who did not require insulin (relative risk=1.5, 95% CI=0.5–3.8, NS). We conclude that the need for bedtime insulin, reflecting persistent fasting hyperglycemia in a GDM pregnancy, is highly predictive for the development of subsequent DM.

Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy.

A reduction in beta-cell mass is an important causative factor in type 1 and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) and the long-acting agonist exendin 4 (Ex-4) expand beta-cell mass by stimulating neogenesis and proliferation. In the partial pancreatectomy (Ppx) model, exogenous Ex-4 promotes islet regeneration, leading to sustained improvement in glucose tolerance. In this study, we investigate the potential role of endogenous GLP-1 in islet growth. We examined beta-cell mass regeneration after 70% Ppx in mice receiving the GLP-1 antagonist Ex9-39 and in GLP-1R(-/-) mice. In Ex9-39-treated sham-operated mice, persistent fasting hyperglycemia was observed, but beta-cell mass was not diminished. In pancreatectomized mice, persistent glucose intolerance was noted, but this was not further exacerbated by Ex9-39. Accordingly, beta-cell mass recovery of Ppx mice was not impaired by Ex9-39. In contrast, GLP-1R(-/-) CD1 mice showed worse glucose intolerance after Ppx compared with wild-type CD1 Ppx mice, and this correlated with a significant defect in beta-cell mass regeneration. The recovery of beta-cell mass differed markedly in the BALB/c and CD1 control mice, indicating a significant role of genetic background in the regulation of beta-cell mass. These studies point to a role for endogenous GLP-1 in beta-cell regeneration after Ppx in mice.

Community-based epidemiological study of glucose tolerance in Kin-Chen, Kinmen: support for a new intermediate classification

In this population-based survey, we investigated the prevalence of varying degrees of glucose tolerance among residents of Kin-Chen, Kinmen, as well as the association of glucose tolerance status with potential risk factors for type 2 diabetes and cardiovascular disease (CVD). We focused particularly on subjects with normal 2-h postload glucose level (<7.8 mmol/l) but persistent fasting hyperglycemia (PFH) (5.6–7.8 mmol/l), to examine whether PFH represents an intermediate state between normal glucose tolerance (NGT) and impaired glucose tolerance (IGT). The target population comprised 6346 residents aged 30 years and older. A total of 4354 subjects could be classified into categories of NGT, PFH, IGT, new diabetes, and known diabetes according to medical history, fasting plasma glucose levels, and the results of a 75-g oral glucose tolerance test (OGTT). The potential cardiovascular risk factors assessed included age, obesity (general and central), systolic blood pressure, and fasting levels of insulin, C-peptide, triglyceride, cholesterol, and high-density lipoprotein cholesterol (HDL-C). The age-standardized prevalences of PFH, IGT, new diabetes, and known diabetes were 2.9%, 3.5%, 4.0%, and 3.0%, respectively. Among nondiabetic subjects, the cardiovascular risk factor profiles worsened with decreasing glucose tolerance, with most values differing significantly among the NGT, PFH, and IGT groups. Subjects with PFH, who would be classified as having NGT according to conventional WHO criteria, had physical and biochemical features between those of the NGT and IGT groups. These findings support our previous observation that PFH may be a transition state between NGT and IGT in the progression toward type 2 diabetes.

Progression to type 2 diabetes among high-risk groups in Kin-Chen, Kinmen. Exploring the natural history of type 2 diabetes.

To examine the natural history of 654 high-risk subjects (340 men and 314 women) with fasting hyperglycemia (first fasting plasma glucose [FPG] level 5.6-7.8 mmol/l) who also exhibited 2-h postload glucose concentrations < 11.1 mmol/l and an FPG level < 7.8 mmol/l in a 75-g oral glucose tolerance test (OGTT). We were particularly interested in comparing the likelihood of developing type 2 diabetes for those with persistent fasting hyperglycemia (PFH), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). PFH is a relatively new definition, and those with PFH used to be defined as NGT according to WHO criteria. Subjects were located in a 1992-1994 community-based population survey and followed up and reexamined during 1995-1996. An OGTT was used to determine who had progressed to type 2 diabetes. Risk factors predictive of subsequent progression to type 2 diabetes were determined by comparing baseline variables from the 1992-1994 survey with data of those who had or had not progressed to type 2 diabetes in 1995-1996. Of 654 high-risk subjects screened in the baseline survey, 481 (73.5%, 255 men and 226 women) were followed up. Of these, 8.1% had progressed to diabetes (4.1% progression/year, 95% CI 2.3-5.9). Of 131 baseline IGT subjects, 17.6% progressed to diabetes (8.8% progression/year, 6.3-11.3), but only 7.4% of 95 PFH subjects (3.7% progression/year, 2.0-5.4) and 3.5% of 255 NGT subjects (1.8% progression/year, 0.1-3.0) progressed to diabetes. The rates of progression to type 2 diabetes were lowest from the NGT subgroup, highest from the IGT group, with the PFH group in the middle, suggesting that PFH might be a transitional condition that precedes IGT and diabetes. Other significant predictors of subsequent diabetes were baseline BMI, baseline hyperuricemia, baseline FPG, and 2-h plasma glucose concentration.

Treatment of Early-Morning Hyperglycemia in Type 1 Diabetics with Amorphous Zinc Insulin (Semilente&amp;reg;) at Bedtime

Fasting hyperglycemia in insulin-dependent diabetic patients (IDDM) treated according to the basal-bolus principle may be due to the fact that currently available neutral protamine Hagedorn (NPH) insulin preparations do not sufficiently meet the increased insulin need in the second part of the night. In the present study, it was investigated whether the amorphous zinc insulin Semilente can be used to control fasting hyperglycemia in IDDM patients. Ten type 1 diabetic patients with persistent fasting hyperglycemia (> 10 mmol/l) participated in the double-blind randomized cross-over trial with 2 10-day treatment periods. Night profiles of blood glucose and free insulin concentrations were determined at the end of each treatment period. Three doses of regular insulin were given before the meals and NPH insulin and Semilente at 10.00 p.m. Nighttime blood glucose and insulin profiles were different under the treatment with Semilente and NPH insulin. Injection of Semilente at bedtime resulted in higher insulin and lower blood glucose values during the second part of the night (p < 0.001 versus Semilente by ANOVA). Semilente injected at bedtime can prevent the early-morning rise in blood glucose in type I diabetic patients.

Prevention of Early-Morning Hyperglycemia in IDDM Patients With Long-Acting Zinc Insulin

To evaluate whether an insulin regimen with a long-acting zinc insulin (Ultratard HM) could help control fasting hyperglycemia in insulin-dependent diabetes mellitus (IDDM) patients. A randomized sequential crossover trial with 6-wk treatment periods was used. Ten IDDM patients from the diabetes clinic at the Medical School who had persistent fasting hyperglycemia (greater than 10 mmol/L) were studied. Patients with nocturnal hypoglycemia were excluded. All patients completed the study. Insulin regimens consisted of three daily injections of a short-acting insulin (Actrapid HM) before meals and either a long-acting zinc insulin (Ultratard HM) or an intermediate isophane insulin (Protaphane HM) before the evening meal. Each regimen was followed for 6 wk. Fasting blood glucose levels (at 06:00 and 08:00) were significantly lower after the long-acting insulin regimen (6.26 +/- 0.88 vs. 10.82 +/- 4.27 mM, P less than 0.05 and 9.26 +/- 1.02 vs. 14.03 +/- 1.08 mM, P less than 0.05, respectively). Plasma-free insulin levels mirrored blood glucose concentrations because they were significantly higher at 06:00 and 08:00 after the long-acting insulin regimen (49.5 +/- 10.1 vs. 20.1 +/- 4.3 pM, P less than 0.05 and 31.6 +/- 5.0 vs. 16.5 +/- 3.4 pM, P less than 0.05, respectively). At any other time of the day, blood glucose and plasma insulin levels were not significantly different with either one of the two insulin regimens. A long-acting zinc human insulin injected before the evening meal can help to control persistent fasting hyperglycemia in IDDM patients.

Oral contraceptive use: Prospective follow-up of women with suspected glucose intolerance

593 women from a cohort of 8,652 healthy women failed a 1-hr glucose screening test. These 593 women with suspected glucose intolerance were classified as normal or as having impaired glucose tolerance (IGT) or diabetes mellitus (DM) after an oral standard glucose tolerance test (SGTT) and were followed over a mean 8.55 years. No permanent change in glucose status as a result of oral contraceptive use was found in an analysis for impaired glucose tolerance, diabetes mellitus, diabetic symptoms, or use of oral agents and/or insulin. Increased glucose intolerance was observed for women who were older, had a positive family history of diabetes, or were of greater relative weight. Diabetic symptoms correlated most closely with the onset of persistent fasting hyperglycemia.

Cirrhosis and diabetes. I. Increased incidence of diabetes in patients with Laennec's cirrhosis.

The frequency of diabetes, defined as persistent fasting hyperglycemia, was evaluated in a consecutive group of 240 cirrhotic patients. A randomly selected group of 411 noncirrhotic patients of similar age, admitted to the hospital during the same period, served as a control group. Diabetes was significantly more common in the cirrhotic group (40 of 240, 16.7%) than in the noncirrhotic group (29 of 411, 7.1%). In the majority, cirrhosis was apparent before the diabetes was detected; in 18% the diabetes was noted first.