Effect of thiazides on blood sugar level in oedematous and non oedematous states.
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Adult↗
SEARCH · PubMed Health
Results for “Prediabetic State”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
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Pre-diabetes, insulin resistance, inflammation and CVD risk.
There is accumulating evidence that insulin resistance in the pre-diabetic state is associated with the presence of additional cardiovascular risk factors and increased incidence of cardiovascular disease (CVD). There is also accumulating evidence indicating that chronic sub-clinical inflammation as measured by such inflammatory markers as C-reactive protein (CRP) is associated with insulin resistance and other features of the insulin resistance syndrome, increased risk of development of type 2 diabetes and increased cardiovascular event risk. Insulin-sensitizing agents may have greater effects in reducing cardiovascular risk than secretagogues in the pre-diabetic state, and glitazones have been found to decrease CRP levels in patients with diabetes. Statins also reduce CRP levels. Efforts to reduce CVD should include increased emphasis on improving glycaemic control, preventing development of diabetes and addressing cardiovascular risk factors in the pre-diabetic state.
Age Factors↗
Global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD: a systematic review and meta-analysis.
BACKGROUND: The presence of diabetes increases the risk of adverse outcomes of patients with non-alcoholic fatty liver disease (NAFLD) even in those with lean or non-obese NAFLD. However, the epidemiological data regarding the prevalence of diabetes and prediabetes in lean or non-obese NAFLD populations remain limited. We assessed the global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD. METHODS: Published studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science databases from the inception of the databases to October 2024. The pooled global prevalence of diabetes or prediabetes in patients with NAFLD was evaluated using random-effects meta-analysis. Subgroup meta-analysis and meta-regression were used to investigate potential sources of heterogeneity. RESULTS: A total of 54 studies involving 146,714 patients with non-obese or lean NAFLD were included. The pooled global prevalence of diabetes among patients with lean or non-obese NAFLD was 15.6% (95% CI 10.8%-22.7%). Studies from South America reported the highest prevalence (41.3%, CI 39.1%-43.5%). Meta-regression models showed that geographic region and mean age (p < 0.05) were associated with the were associated with the prevalence of diabetes, jointly accounting for 51.61% of the heterogeneity. The global prevalence of prediabetes among patients with lean or non-obese NAFLD was 22.9% (95% CI 12.5%-41.9%) with the highest prevalence reported in studies from Europe (34.4%, CI 23.0%-51.4%). Meta-regression models showed that geographic region and country (p < 0.05) were associated with the prevalence of prediabetes, jointly accounting for 73.65% of the heterogeneity. CONCLUSION: The pooled global prevalence of diabetes and prediabetes were 15.6% and 22.9% in lean or non-obese patients with NAFLD, respectively. These findings suggest the importance of diabetes screening in these patients.
Humans↗
User Engagement and Feature Preferences in an AI-Powered mHealth Intervention for Diabetes Prevention: Secondary Analysis of a Randomized Controlled Trial.
BACKGROUND: Prediabetes is highly prevalent and increasing globally, yet lifestyle interventions remain underused. AI-driven mobile health (mHealth) tools can help scale diabetes prevention efforts, but the key factors driving their success are not well understood. OBJECTIVE: This post hoc secondary analysis of a randomized controlled trial (RCT) aimed to characterize the most valued features and the role of user engagement in outcomes of a fully automated mHealth intervention for diabetes prevention. METHODS: Data from 151 participants with prediabetes and overweight or obesity who were assigned to an AI-based diabetes prevention program (Sweetch) in a parent RCT (NCT05056376) were analyzed. Engagement (defined as the total number of days the app was used) was categorized into tertiles (low, medium, and high). Baseline characteristics were compared across engagement groups using ANOVA, Kruskal-Wallis, and chi-square tests, and regression models assessed the association between engagement and achievement of diabetes risk reduction outcomes (≥5% weight loss, ≥4% weight loss with ≥150 min/week of physical activity, or ≥0.2 percentage point reduction in hemoglobin A1c [HbA1c] at 12 months). Perceived usefulness of intervention features was surveyed at 12 months. RESULTS: Median engagement was 98 (IQR 34-232) days. Older age (P<.001) and lower baseline BMI (P=.04) were significantly associated with higher engagement. Compared with low engagement, high engagement was associated with greater odds of achieving the composite diabetes risk reduction outcome (odds ratio [OR] 2.59, 95% CI 1.11-6.01; P=.03), ≥5% weight loss (OR 3.31, 95% CI 1.16-9.42; P=.03), and ≥0.2 percentage point reduction in HbA1c (OR 3.57, 95% CI 1.19-10.75; P=.02). Participants most frequently rated weight tracking, physical activity tracking, and the digital body weight scale as the features that were most helpful for achieving their health goals. CONCLUSIONS: Higher engagement with an AI-driven intervention requiring no human intervention was associated with improved diabetes risk reduction. Contrary to concerns about lower digital literacy, older adults engaged with the intervention more than younger adults. Features related to weight and physical activity tracking were most valued by patients in the program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05056376; https://clinicaltrials.gov/study/NCT05056376.
Humans↗
Pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus: candidates for a signal transmitter defect causing insulin resistance of the skeletal muscle.
Insulin resistance of skeletal muscle, liver and fat combined with an abnormality of insulin secretion characterizes Type 2 (non-insulin-dependent) diabetes mellitus. There is increasing evidence that the insulin resistance of the skeletal muscle plays a key role early in the development of Type 2 diabetes. As a consequence recent research efforts have focussed on the characterization of insulin signal transduction elements in the muscle which are candidates for a localization of a defect causing insulin resistance i.e. the insulin receptor, phosphatases related to insulin action, glycogen synthase and the glucose transporters. In this review we attempt to summarize present knowledge about abnormalities of these systems in skeletal muscle of Type 2 diabetic and pre-diabetic individuals. We try to classify abnormalities as secondary events or as candidates for putative primary molecular defects which might initiate the development of insulin resistance as early as in the "pre-diabetic" state.
Animals↗
Early Cardiomyopathy in Prediabetic NDPK-B-Deficient Mice Is Associated with Remodeling of the Mitochondrial O-GlcNAc Proteome.
Diabetic cardiomyopathy (DCM) is characterized by myocardial remodeling that may already be evident during prediabetes, yet the molecular alterations accompanying these early changes remain poorly understood. The present study examined mouse models of Nucleoside diphosphate kinase B (NDPK-B)-deficient prediabetes and streptozotocin-induced diabetes using O-GlcNAc-associated proteomic profiling to define stage-specific molecular alterations during the progression from prediabetic to diabetic cardiomyopathy. Both models exhibited increased left ventricular extracellular matrix deposition and impaired diastolic function, together with activation of the hexosamine biosynthesis pathway. Profiling of O-GlcNAc-associated proteins uncovered extensive remodeling of the mitochondrial proteome already at the prediabetic stage, with respiratory complex I among the most prominently altered targets, alongside changes in substrate metabolism and inflammatory signaling. In overt DCM, the putative O-GlcNAc proteomic profile was associated with a shift toward wider lipid-dependent metabolic reprogramming and remodeling of mitochondrial proteins. These findings identify early remodeling of the mitochondrial O-GlcNAc-associated proteome as a molecular signature of prediabetic cardiomyopathy and highlight respiratory complex I proteins as candidate targets for future mechanistic investigations.
Animals↗
Effects of time-restricted eating on markers of glucose metabolism and regulation in individuals with prediabetes or type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.
AIMS/HYPOTHESIS: This systematic review and meta-analysis aimed to investigate the effects of time-restricted eating (TRE) on glucose metabolism and regulation in individuals with prediabetes (fasting blood glucose of 5.6-6.9 mmol/l or HbA1c of 39-47 mmol/mol [5.7-6.4%]) or type 2 diabetes (fasting blood glucose ≥7 mmol/l or HbA1c ≥48 mmol/mol [6.5%]). METHODS: A literature search was performed in MEDLINE, Embase and CENTRAL from inception to 5 August 2025. Moreover, forward and backward citation searches were performed. Eligible studies were RCTs in adults with prediabetes or type 2 diabetes, lasting ≥2 weeks, reporting markers of glucose metabolism and regulation, comparing TRE (≤12 h eating window) with a non-time-restricted control diet. Studies involving pregnancy, other fasting regimens, or non-peer-reviewed publications were excluded. Data were pooled as weighted mean differences with 95% CIs using random-effects generic inverse variance models in Cochrane Review Manager Web, and results are presented as forest plots. The certainty of evidence was defined using Grading of Recommendations, Assessment, Development and Evaluations methodology, and risk of bias was estimated by using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). RESULTS: Out of 2043 records identified through the database search, as well as 1249 from forward and backward citation searches, ten RCTs including 599 participants were included. The mean length of the studies was 4 months, and the eating windows ranged from 4 to 10 h per day. The pooled meta-analysis showed no overall effect of TRE on HbA1c (-3.33 mmol/mol; 95% CI -6.87, 0.20 (-0.30% points; -0.63, 0.02); p=0.06, moderate certainty). Nevertheless, following stratification by subgroups, TRE resulted in a reduction in HbA1c of 0.93 mmol/mol (-1.70, -0.17 [-0.09% points; -0.16, -0.02]; p=0.02) in individuals with prediabetes but not in individuals with type 2 diabetes (-4.68 mmol/mol; -10.08, 0.72 (-0.43% points; -0.92, 0.07); p=0.09). TRE reduced fasting blood glucose in the pooled analysis (-0.30 mmol/l; -0.53, -0.07; p<0.01, moderate certainty) as well as in the subgroup analyses in individuals with prediabetes (-0.14 mmol/l; -0.27, -0.01; p=0.03) and with type 2 diabetes (-0.48 mmol/l; -0.78, -0.17; p<0.01). Moreover, TRE lowered body weight by 1.6 kg (-2.2, -1.0; p<0.001) in the pooled analysis. The evidence was limited by imprecision arising from wide confidence intervals in some of the included studies, which may be due to small sample sizes. Lastly, the effects of TRE on markers of insulin sensitivity, beta cell function and continuous glucose monitoring measurements were inconclusive. CONCLUSIONS/INTERPRETATION: Moderate-certainty evidence indicates that TRE reduces fasting blood glucose but not HbA1c. The subgroup analyses revealed that TRE improved HbA1c and fasting glucose in individuals with prediabetes and improved fasting glucose in individuals with type 2 diabetes. Future large-scale studies should investigate long-term effects of TRE in prevention and treatment of type 2 diabetes. TRIAL REGISTRATION: PROSPERO CRD42024523591 FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Three authors (JS, A-DT, THA) are employed at Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, partly funded by a grant from the Novo Nordisk Foundation.
Humans↗
[Autosomal dominant mild juvenile diabetes mellitus (MODY) (author's transl)].
A family is described in which eleven members, over four generations, suffer from the autosomal dominant inherited maturity onset type diabetes of young people (MODY). A comparison of these findings with those of six families previously described in the literature shows in particular that: 1. manifestation of the disease is predominantly at a fairly young age, 2. the complaint is not insulin-dependent nor is it progressive, 3. when medical supervision is adequate, there are hardly any secondary complications, 4. the inheritance pattern is autosomal dominant with high penetrance and probably a stronger expressivity in the female. This disease can be separated from the classical, insulin-dependent diabetes of the young, from the autosomal dominant lipatrophic diabetes and from the heterozygous form of the autosomal recessive complaint, which in the homozygous state shows diabetes mellitus and insipidus with optic atrophy.
Adolescent↗
Identifying the pre-diabetic state in type I diabetics: condition for early intervention.
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Autoantibodies↗
[Pathogenesis of diabetes in adulthood. I. Insulin secretion at different evolutionary phases of diabetes].
Intravenous loading with glucose and glucose+tolbutamid was conduced in five groups of subjects, selected in a way that the intensity of insulin secretion gradually decreases from one group to the other (control group, relatives of patients with diabetes, diabetics sensitive to SUP and diabetics resistant to SUP). With insulin deficiency (in the last three groups) the early insulin secretion (absence of summit in IRI curve at the tenth minute), was established to grow weak, whereas in latent diabetes and in SUP sensitive diabetics it was preserved and insulinemia was protracted during the second half of the test. Early insulin secretion, in the control group and in the relatives of the diabetics, with loading with glucose-tolbutamid was twice as high as compared with that, obtained with loading solely with glucose. Diabetes at a mature age is concluded to be with a changed sensitivity of B-cells, at the beginning, versus glucose as a stimulator with signaling character, but the ability for synthesis and secretion of insulin, in general, is preserved. With the evolution of diabetes defect, the falling-off of insulin-synthesis ability is included in the pathogenetic mechanisms. A state of complete insulin deficiency develops--hence non-sensitivity to SUP.
Adult↗
[Some changes in lipid metabolism and the state of the vascular wall in rats with a prolonged course of alloxan diabetes].
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Animals↗
Molecular Signature of Prediabetes With High-Risk of Diabetes Revealed by Deep Plasma Proteome.
AIMS: Prediabetes is biologically heterogeneous, but molecular subtypes linked to diabetes progression remain poorly defined. We aimed to identify plasma proteome-based subtypes of impaired fasting glucose (IFG), characterise their molecular features and assess their association with future diabetes risk. MATERIALS AND METHODS: We quantified 2584 plasma proteins using liquid chromatography-mass spectrometry in 538 IFG participants from a prospective discovery cohort (Nutrition and Health of Aging Population in China, NHAPC). Proteomic subtypes were defined by consensus clustering, linked to longitudinal changes in insulin sensitivity and incident type 2 diabetes mellitus (T2DM), which were further validated in an independent Shanghai Brain Aging Study (SBAS) cohort. RESULTS: Two reproducible IFG molecular subtypes based on plasma proteomics were identified. The high-risk subtype showed higher incident diabetes and a greater 6-year decline in insulin sensitivity and was characterised by enrichment of glycolysis/gluconeogenesis, insulin signalling and neutrophil degranulation, together with a dyslipidemic lipidomic profile indicating co-dysregulation of glucose and lipid homeostasis. The low-risk subtype demonstrated a higher complement cascade and high-density lipoprotein particle remodelling signature. In the high-risk subtype, key proteins and lipids showed stronger associations with longitudinal declines in insulin sensitivity, including PPBP, PGK1 and ALDOA, as well as PE-P 18:0/20:3 and PE-P 18:1/20:3. CONCLUSIONS: Proteome-based molecular subtyping stratifies IFG individuals with similar fasting glucose levels but distinct biology and future diabetes risk, supporting earlier and more targeted prevention.
Humans↗
Acute mild cold exposure with shivering reduces 24 h glucose levels in individuals with type 2 diabetes but not prediabetes.
AIMS/HYPOTHESIS: Repeated cold exposure with shivering has been proposed as a potential strategy to enhance glucose metabolism by increasing energy expenditure and substrate utilisation. However, acute effects/benefits of cold-induced shivering on glucose homeostasis in metabolically compromised individuals are unknown. Here, we aimed to determine whether cold exposure at two different intensities improves 24 h glucose homeostasis in individuals with prediabetes and type 2 diabetes. METHODS: In a randomised crossover trial conducted in the South Limburg/Maastricht region of the Netherlands, men and postmenopausal women with prediabetes (n=12) and stable type 2 diabetes (n=12), aged 40-75 years, body mass index ≥27 and ≤35 kg/m2, non-smoking and sedentary, underwent two whole-body cold exposure sessions using a water-perfused suit. Session order was randomised using an online randomisation tool (randomizer.org); participants were masked to the cold exposure intensity received, but investigators were not. Sessions were designed to elicit ~1.5-fold (mild, 15°C) and ~2.5-fold (moderate, 4°C) increases in resting metabolic rate (RMR). Continuous glucose monitoring assessed interstitial glucose concentrations over 24 h periods before and after each intervention, with controlled diet and activity. Shivering was confirmed via indirect calorimetry and electromyography. RESULTS: In both study groups and periods, RMR increased significantly vs baseline (p<0.001 for all). In prediabetes, the increase in the final 1 h of cold was 1.53 × RMR in mild and 1.94 × RMR in moderate cold. In type 2 diabetes, the increase was 1.57 × RMR and 2.09 × RMR in the final 1 h of mild and moderate cold, respectively. In prediabetes, neither mild nor moderate cold exposure altered mean 24 h glucose levels. In contrast, after mild cold exposure the type 2 diabetes group exhibited a significant reduction in mean 24 h glucose levels (-0.6 ± 0.5 mmol/l, p=0.003) and fasting glucose (-0.6 ± 0.8 mmol/l, p=0.019), as well as an increase in time in normal range (+8.8 ± 10.3%, p=0.013) and reduced time in hyperglycaemia (-10.9 ± 12.9%, p=0.014). Moderate cold did not significantly affect any of the glucose outcomes in type 2 diabetes. Baseline fasting glucose, age and ALT levels were predictors of the glucose-lowering response, suggesting greater benefits in individuals who have higher baseline glucose levels, are younger and/or have more optimal liver health, i.e. lower ALT. CONCLUSIONS/INTERPRETATION: Acute mild cold exposure with shivering reduced 24 h glucose levels in individuals with type 2 diabetes. No changes were observed in prediabetes. The observed effects appear to depend on baseline metabolic status rather than acute substrate utilisation during cold exposure. These findings support the potential of cold exposure as an adjunct non-pharmacological therapy for type 2 diabetes, although further mechanistic studies and validation in larger cohorts are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576025 FUNDING: Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-being (ZonMw): 09120012010062.
Humans↗
Assessing progression to impaired glucose tolerance and type 2 diabetes mellitus.
BACKGROUND: A prospective evaluation of the relationship between insulin secretion and insulin sensitivity, derived from the fasting state, is needed in clinical practice in order to identify the worsening of glucose metabolism. In this study the authors examine whether the product of insulin sensitivity and insulin secretion, assessed from the fasting state, predicts progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) and from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A cohort of 300 subjects with NGT and 75 subjects with IGT were followed up over a 5-year period. Insulin sensitivity was calculated using the Belfiore index (B) and insulin secretion by the homeostasis model analysis beta-cell (HOMA-beta cell) index: the product of B-beta is expressed as: (40 x Ins(0) pmol L(-1))/Glu(0) mmol L(-1){[(Glu(0) mmol L(-1)x Ins(0) pmol L(-1)) + 1] - 3.5[(Glu(0) mmol L(-1) x Ins(0) pmol L(-1)) - 1]}, where Glu(0) is fasting glucose and Ins(0) is fasting insulin. RESULTS: From baseline at the end of the follow-up period, the product B-beta decreased 10.7% and 52.2% in progressors to IGT and T2DM, respectively. The product B-beta predicts the progression from NGT to IGT [relative risk (RR) 2.7, CI(95%) 1.2-9.1] and from IGT to T2DM (RR 5.3, CI(95%) 1.3-8.55). The cut-off point for the product B-beta that better predicts progression from NGT to IGT is 0.25 (sensitivity 88%, specificity 92%) and from IGT to T2DM 0.15 (sensitivity 92%, specificity 95%). CONCLUSIONS: Adaptation of insulin secretion to compensate for decreased insulin sensitivity during transition to IGT and T2DM can be successfully assessed with simple measures derived from the fasting state. The product B-beta predicts the development to IGT and T2DM.
Adult↗
[Immunotherapy of type 1 diabetes].
Insulin-dependent diabetes mellitus is the late consequence of a chronic autoimmune disease directed to the B islet cell, that begins long before the hyperglycemic state. Experimental evidence suggests a central pathogenic role for autoreactive T lymphocytes. Immunointervention studies, particularly those using cyclosporin, have shown that it is possible to stop B cell destruction, even at the late stage of overt diabetes. New therapeutic approaches will be focused on the use of specific agents such as monoclonal antibodies and immunotoxins, and on earlier interventions allowed by the detection of genetic and immunological markers of prediabetes.
Diabetes Mellitus, Type 1↗
Impact of pre-diabetic state on clinical outcomes in patients with acute coronary syndrome.
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Aged↗
Interleukin-1 effect on glycemia in the non-obese diabetic mouse at the pre-diabetic stage.
Cytokines, particularly interleukin 1 (IL-1) and tumor necrosis factor, are known to induce hypoglycemia in normal rodents or different experimental models of type II diabetes. We investigated, at the pre-diabetic stage, the effect of short-term administration of murine recombinant interleukin-1 alpha (mrIL-1 alpha) on the levels of glucose, insulin and corticosterone in the non-obese diabetic (NOD) mouse, a spontaneous model of type I diabetes. Two-month-old, pre-diabetic NOD mice of both sexes were insensitive to mrIL-1 alpha (12.5 and 50 micrograms/kg) 2 h after administration, the time at which the maximal decrease (around 50%) was observed in the C57BL/6 mouse strain. Kinetic studies however showed that mrIL-1 alpha lowered glycemia in both sexes of NOD mice, but the effect was limited and delayed. In the NOD and C57BL/6 strains, mrIL-1 alpha had no influence on insulin levels in females, but significantly increased them in males (P < 0.0001). Castration of NOD males abrogated the stimulatory effect of mrIL-1 alpha on insulin secretion. Corticosterone secretion was stimulated by mrIL-1 alpha in both sexes of NOD and C57BL/6 mice, and this effect was faster and greater in NOD females than in C57BL/6 females. The incomplete hypoglycemic response to mrIL-1 alpha in females may be attributed to the anti-insulin effect of glucocorticoids, an effect which can be demonstrated when mrIL-1 alpha is administered to adrenalectomized animals or when mrIL-1 alpha is administered together with the glucocorticoid antagonist RU38486. In NOD males, in contrast, glucocorticoids did not play a major role in the limited hypoglycemic response to mrIL-1 alpha, since RU38486 and adrenalectomy were not able to unmask a hypoglycemic effect. Moreover, NOD mice of both sexes were less sensitive than C57BL/6 mice to the hypoglycemic effect of insulin (2.5 U/kg), which suggests some degree of insulin-resistance in NOD mice. With regard to the effect of IL-1 on NOD mouse glycemia, therefore, these results suggest that glucocorticoids and/or androgens, according to the animal's sex, may induce a state of insulin-resistance.
Adrenalectomy↗
[Pathophysiology of insulin resistance].
Insulin resistance of skeletal muscle, liver and fat combined with an abnormality of insulin secretion characterizes Type 2 (non-insulin-dependent) diabetes mellitus. There is increasing evidence that the insulin resistance of the skeletal muscle plays a key role early in the development of Type 2 diabetes. As a consequence recent research efforts have focussed on the characterization of insulin signal transduction elements in the muscle which are candidates for a localization of a defect causing insulin resistance, i.e. the insulin receptor, phosphatases related to insulin action, glycogen synthase and the glucose transporters. In this review we attempt to summarize present knowledge about abnormalities of these systems in skeletal muscle of Type 2 diabetic and pre-diabetic individuals. We try to classify abnormalities as secondary events or as candidates for putative primary molecular defects which might initiate the development of insulin resistance as early as in the "pre-diabetic" state. Insulin resistance is combined with abnormalities of insulin secretion. Compensatory hypersecretion of insulin is typically found in early stages of the development of the "Metabolic Endocrine Syndrome" and the pre-diabetic state. The transition from this pre-diabetic state to the clinically overt Type 2 diabetes is accompanied or even caused by declining insulin secretion. The molecular mechanism causing declining insulin secretion is not understood in detail. Beside genetically determined factors regulatory events might be important.
Adipose Tissue↗