|
1
|
Phate NG, Kumar S, Acharya S, Agrawal SR, Wanjari A, Wakode M, Gemnani RR. Ankle brachial index and its correlation with cardiovascular risk factors in pre-diabetes: Two-year cross-sectional study. J Family Med Prim Care 2023; 12:2894-2902. [PMID: 38186819 PMCID: PMC10771145 DOI: 10.4103/jfmpc.jfmpc_227_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 06/21/2023] [Accepted: 06/26/2023] [Indexed: 01/09/2024] Open
Abstract
Background A state of impaired glucose tolerance is called prediabetes. The diagnosis of prediabetes is controversial, yet it still puts a person at risk for developing diabetes. The ankle-brachial index (ABI) is useful for identifying persons at risk for peripheral artery disease and for diagnosing the condition in those who have symptoms in their lower extremities and subclinical atherosclerosis. This study highlights ABI and its correlation with cardiovascular risk factors like lipid profile and anthropometric measurement including neck circumference in prediabetes so that primary care physicians may be able to diagnose early before advancing to diabetes. Materials and Methods This cross-sectional study of 2 years duration from December 2020 to September 2022 was conducted in the Department of Medicine, at a tertiary care teaching hospital situated in a rural area. Patients with pre-diabetes were enrolled and Ankle Brachial Index was calculated. The correlation of ABI with anthropometric measures and lipid profile was assessed. Results On calculating ABI by manual method 21% which is 42 out of 200 had low ABI (<0.9). On the other hand, on calculating ABI by probe method low range of ABI was found to be 37% which is 74 patients out of 200. There was a significant correlation between ABI and body mass index and lipid profile. The diagnostic performance of ABI < 0.9 had 56.8% sensitivity and 100.0% specificity. Conclusion ABI can be used as a noninvasive and cost-effective modality for assessing subclinical atherosclerosis in patients with prediabetes and thus prevent its morbid complications even assessed at the primary care physician level.
Collapse
Affiliation(s)
- Neha G. Phate
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
| | - Sunil Kumar
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
| | - Sourya Acharya
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
| | - Sachin R. Agrawal
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
| | - Anil Wanjari
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
| | - Monish Wakode
- Department of Medicine, NKP Salve Institute of Medical Sciences, Nagpur, Maharashtra, India
| | - Rinkle R. Gemnani
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Wardha, Maharashtra, India
| |
Collapse
|
|
2
|
Hu Z, Hou J, Zhang M. Levels of inter-alpha-trypsin inhibitor heavy chain H4 urinary polypeptide in gestational diabetes mellitus. Syst Biol Reprod Med 2021; 67:428-437. [PMID: 34607479 DOI: 10.1080/19396368.2021.1977869] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Gestational diabetes mellitus (GDM) can cause a variety of adverse maternal and fetal complications. The purpose of this study was to screen and identify the urinary polypeptides related to the severity of GDM and to analyze the correlation between urinary peptide levels and neonatal metabolic indices. A total of 31 normal pregnant women (N group) and 74 patients with GDM (GDM group) were randomly selected between February 2018 and August 2019. Patients with GDM were divided into two groups according to their fasting plasma glucose (FPG) levels. The urine samples were enriched using weak cation-exchange magnetic beads (MB-WCX), and eight different urine polypeptides were screened and analyzed. The peptide spectra were obtained using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The urinary peptide signatures of the two groups were compared using the BioExplorer software. The difference analysis of the eight urinary polypeptides between the normal pregnant (N) group and GDM group showed that two polypeptides with mass-to- charge ratios (m/z) of 2175.7 and 2318.8, respectively, were significantly different between the two groups (P < 0.01). The m/z 2175.7 polypeptide was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS), and the corresponding name of the molecule was inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). The changes in ITIH4 levels correlated with those in the neonatal metabolic indices. By establishing the Fisher discriminant function equation for the GDM group, the difference in sample distribution and mean value of the two groups could be observed directly.Abbreviations: GDM: gestational diabetes mellitus; FPG: fasting plasma glucose; MB-WCX: weak cation exchange magnetic beads; MALDI-TOF MS: matrix-assisted laser desorption ionization time-of-flight mass spectrometry; m/z: mass charge ratio; LC-MS: liquid chromatography-tandem mass spectrometry; glycosylated hemoglobin (HbA1c); PPG: postprandial plasma glucose; ITIH4: inter-alpha-trypsin inhibitor heavy chain H4; IR: insulin resistance; NFPG: neonatal fasting plasma glucose; NH: neonatal height; NW: neonatal weight; BMI: body mass index; RPL: recurrent pregnancy loss; OGTT: oral glucose tolerance test; ADA: American Diabetes Association; LIS: Laboratory Information System.
Collapse
Affiliation(s)
- Zhiying Hu
- Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China
| | - Junlin Hou
- Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China
| | - Man Zhang
- Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China
| |
Collapse
|
|
3
|
A Newly Developed Diabetes Risk Index, Based on Lipoprotein Subfractions and Branched Chain Amino Acids, is Associated with Incident Type 2 Diabetes Mellitus in the PREVEND Cohort. J Clin Med 2020; 9:jcm9092781. [PMID: 32867285 PMCID: PMC7563197 DOI: 10.3390/jcm9092781] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/12/2020] [Accepted: 08/23/2020] [Indexed: 12/15/2022] Open
Abstract
Objective: Evaluate the ability of a newly developed diabetes risk score, the Diabetes Risk Index (DRI), to predict incident type 2 diabetes mellitus (T2D) in a large adult population. Methods: The DRI was developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from 6 lipoprotein subspecies and size parameters, and the branched chain amino acids, valine and leucine, all of which have been shown previously to be associated with future T2D. DRI scores were calculated in a total of 6134 nondiabetic men and women in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident T2D. Results: During a median follow-up of 8.5 years, 306 new T2D cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI scores and incident T2D with the hazard ratio (HR) for the highest versus lowest quartile being 12.07 (95% confidence interval: 6.97–20.89, p < 0.001). After additional adjustment for body mass index (BMI), family history of T2D, alcohol consumption, diastolic blood pressure, total cholesterol, triglycerides, HDL cholesterol and HOMA-IR, the HR was attenuated but remained significant (HR 3.20 (1.73–5.95), p = 0.001). Similar results were obtained when DRI was analyzed as HR per 1 SD increase (HR 1.37 (1.14–1.65), p < 0.001). The Kaplan–Meier plot demonstrated that patients in the highest quartile of DRI scores presented at higher risk (p-value for log-rank test <0.001). Conclusions: Higher DRI scores are associated with an increased risk of T2D. The association is independent of clinical risk factors for T2D including HOMA-IR, BMI and conventional lipids.
Collapse
|
|
4
|
Anderson P, Grills N, Singh R, Singh R, Evans RG, Sengupta P, Thrift AG. Prevalence of diabetes and pre-diabetes in rural Tehri Garhwal, India: influence of diagnostic method. BMC Public Health 2019; 19:817. [PMID: 31234815 PMCID: PMC6591826 DOI: 10.1186/s12889-019-7184-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 06/17/2019] [Indexed: 01/14/2023] Open
Abstract
Background There are few available data regarding the prevalence of diabetes in the sub-Himalayan region of India. The aim of this study was to determine the prevalence of pre-diabetes and diabetes in rural Garhwal based on glycosylated hemoglobin. Methods In a cross-sectional survey of 500 adults from five randomly selected villages in Chamba, a mountainous Tehri Garhwal district in Uttarakhand in north-west India, we determined the prevalence of diabetes (hemoglobin (Hb) A1c ≥ 6.5%) and pre-diabetes (5.7% ≤ HbA1c ≤ 6.4%). In a sub-sample of those diagnosed with diabetes or pre-diabetes (n = 140), fasting blood glucose (FBG, n = 117) or postprandial blood glucose (PBG, n = 23), and blood hemoglobin concentration, was measured at follow-up. Results Based on HbA1c, 10.0% had diabetes and 56.4% pre-diabetes. Of those diagnosed as diabetic by HbA1c, 10 of 16 (62.5%) were diagnosed as diabetic by FBG (> 125 mg/dL) or PBG (≥200 mg/dL). In those diagnosed as pre-diabetic by HbA1c, only 55 of 124 (44.4%) were diagnosed as pre-diabetic by FBG (100–125 mg/dL) or PBG (140–199 mg/dL). A large proportion of these 140 individuals (67.1%) were moderately to severely anemic (Hb < 11.4 mg/dL). The diagnostic gap for pre-diabetes between HbA1c and FBG/PBG was similar for the groups with and without moderate to severe anemia. Conclusions HbA1c and FBG/PBG have similar diagnostic performance for diabetes in this population. However, many individuals were diagnosed with pre-diabetes by HbA1c but not FBG/PBG. The relative excess diagnosis of pre-diabetes with HbA1c does not appear to be explained by anemia, an endemic condition in India. The prognostic significance of diagnosis of pre-diabetes by HbA1c but not FBG/PBG remains unknown, but merits investigation. Electronic supplementary material The online version of this article (10.1186/s12889-019-7184-4) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Pam Anderson
- Nossal Institute for Global Health, University of Melbourne, Melbourne, Australia
| | - Nathan Grills
- Nossal Institute for Global Health, University of Melbourne, Melbourne, Australia
| | - Rajesh Singh
- Garhwal Community Development and Welfare Society, Mussoorie Road, Chamba, India
| | - Rajkumari Singh
- Garhwal Community Development and Welfare Society, Mussoorie Road, Chamba, India
| | - Roger G Evans
- Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria, Australia
| | | | - Amanda G Thrift
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, 3800, Australia.
| |
Collapse
|
|
5
|
Flores-Guerrero JL, Connelly MA, Shalaurova I, Gruppen EG, Kieneker LM, Dullaart RPF, Bakker SJL. Lipoprotein insulin resistance index, a high-throughput measure of insulin resistance, is associated with incident type II diabetes mellitus in the Prevention of Renal and Vascular End-Stage Disease study. J Clin Lipidol 2018; 13:129-137.e1. [PMID: 30591414 DOI: 10.1016/j.jacl.2018.11.009] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 11/20/2018] [Accepted: 11/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Early assessment of insulin resistance may be a way of identifying patients at risk as well as monitoring treatments that increase insulin sensitivity and reduce the risk of developing type II diabetes mellitus (T2DM). OBJECTIVE The objective of the study was to evaluate the ability of the Lipoprotein Insulin Resistance Index (LP-IR) to predict incident T2DM in a large cohort. METHODS LP-IR scores were calculated using 6 lipoprotein particle concentrations and sizes measured by nuclear magnetic resonance spectroscopy. In total, 5977 nondiabetic men and women were included. Cox proportional hazards regression was used to evaluate the association of LP-IR scores with incident T2DM. RESULTS LP-IR scores were closely associated with insulin resistance, assessed by homeostatic model assessment of insulin resistance (r = 0.51; P < .0001). During a median follow-up for 7.5 years, 278 new T2DM cases were ascertained. The Kaplan-Meier plot with log-rank test (P < .001) demonstrated that elevated LP-IR levels are associated with an increased T2DM risk. In analyses adjusted for age and sex, LP-IR was associated with incident T2DM; hazard ratio (HR) for the highest versus lowest quartile was 10.18 (95% confidence interval: 6.24-16.61), P < .0001. After adjustment for clinical risk factors, the HR was attenuated but remained significant (HR 3.02 [1.73-5.25], P < .0001). LP-IR scores added significantly to the performance of the Framingham Offspring prediction algorithm; C-index (95% confidence interval) for the Framingham Offspring score without and with LP-IR (0.863 [0.863-0.864] and 0.868 [0.867-0.86], P < .0001). Similar results were observed when LP-IR was analyzed as a categorical variable with a clinical cut-point of 68. CONCLUSION LP-IR may be a convenient way to assess insulin resistance and T2DM risk, as well as to monitor preventative treatments.
Collapse
Affiliation(s)
- Jose L Flores-Guerrero
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
| | - Margery A Connelly
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC, USA
| | - Irina Shalaurova
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC, USA
| | - Eke G Gruppen
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Lyanne M Kieneker
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Robin P F Dullaart
- Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Stephan J L Bakker
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| |
Collapse
|
|
6
|
Diagnostic Accuracy of Protein Glycation Sites in Long-Term Controlled Patients with Type 2 Diabetes Mellitus and Their Prognostic Potential for Early Diagnosis. Pharmaceuticals (Basel) 2018; 11:ph11020038. [PMID: 29710851 PMCID: PMC6027301 DOI: 10.3390/ph11020038] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 04/24/2018] [Accepted: 04/24/2018] [Indexed: 12/23/2022] Open
Abstract
Current screening tests for type 2 diabetes mellitus (T2DM) identify less than 50% of undiagnosed T2DM patients and provide no information about how the disease will develop in prediabetic patients. Here, twenty-nine protein glycation sites were quantified after tryptic digestion of plasma samples at the peptide level using tandem mass spectrometry and isotope-labelled peptides as internal standard. The glycation degrees were determined in three groups, i.e., 48 patients with a duration of T2DM exceeding ten years, 48 non-diabetic individuals matched for gender, BMI, and age, and 20 prediabetic men. In long-term controlled diabetic patients, 27 glycated peptides were detected at significantly higher levels, providing moderate diagnostic accuracies (ACCs) from 61 to 79%, allowing a subgrouping of patients in three distinct clusters. Moreover, a feature set of one glycated peptides and six established clinical parameters provided an ACC of 95%. The same number of clusters was identified in prediabetic males (ACC of 95%) using a set of eight glycation sites (mostly from serum albumin). All patients present in one cluster showed progression of prediabetic state or advanced towards diabetes in the following five years. Overall, the studied glycation sites appear to be promising biomarkers for subgrouping prediabetic patients to estimate their risk for the development of T2DM.
Collapse
|
|
7
|
Bansal N. Prediabetes diagnosis and treatment: A review. World J Diabetes 2015; 6:296-303. [PMID: 25789110 PMCID: PMC4360422 DOI: 10.4239/wjd.v6.i2.296] [Citation(s) in RCA: 311] [Impact Index Per Article: 31.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 10/10/2014] [Accepted: 12/31/2014] [Indexed: 02/05/2023] Open
Abstract
Prediabetes is an intermediate state of hyperglycemia with glycemic parameters above normal but below the diabetes threshold. While, the diagnostic criteria of prediabetes are not uniform across various international professional organizations, it remains a state of high risk for developing diabetes with yearly conversion rate of 5%-10%. Observational evidence suggests as association between prediabetes and complications of diabetes such early nephropathy, small fiber neuropathy, early retinopathy and risk of macrovascular disease. Several studies have shown efficacy of lifestyle interventions with regards to diabetes prevention with a relative risk reduction of 40%-70% in adults with prediabetes. While there is increasing evidence to prove the efficacy of pharmacotherapy in prevention of diabetes in adults with prediabetes, pharmaceutical treatment options other than metformin are associated with adverse effects that limit their use for prediabetes. There are no reports of systematic evaluation of health outcomes related to prediabetes in children. The effects of pharmacotherapy of prediabetes on growth and pubertal development in children remains unknown. Secondary intervention with pharmacotherapy with metformin is advocated for high-risk individuals but criteria for such consideration benefit of early intervention, long term cost effectiveness of such interventions and the end point of therapy remain unclear. Pharmacotherapy must be used with caution in children with prediabetes. Prediabetes is a condition defined as having blood glucose levels above normal but below the defined threshold of diabetes. It is considered to be an at risk state, with high chances of developing diabetes. While, prediabetes is commonly an asymptomatic condition, there is always presence of prediabetes before the onset of diabetes. The elevation of blood sugar is a continuum and hence prediabetes can not be considered an entirely benign condition. This aim of this review is to describe the challenges associated with diagnosis of prediabetes, the possible adverse medical outcomes associated with prediabetes and the treatment options and rationale for their use in context of prediabetes.
Collapse
|
|
8
|
Shalaurova I, Connelly MA, Garvey WT, Otvos JD. Lipoprotein insulin resistance index: a lipoprotein particle-derived measure of insulin resistance. Metab Syndr Relat Disord 2014; 12:422-9. [PMID: 24959989 DOI: 10.1089/met.2014.0050] [Citation(s) in RCA: 126] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
UNLABELLED Abstract Background: Lipoprotein particle sizes and concentrations are characteristically altered in patients with insulin resistance (IR) or type 2 diabetes mellitus (T2DM). This study assessed the ability of an IR score, based on nuclear magnetic resonance (NMR)-derived lipoprotein information, to detect IR in otherwise healthy individuals. METHODS Lipoprotein subclass and size information were evaluated for strength of association with IR, as measured by homeostasis model assessment of insulin resistance (HOMA-IR) in the Multi-Ethnic Study of Atherosclerosis (MESA). To increase the likelihood of identifying subjects with IR, six lipoprotein measures were combined into a single algorithm. The resulting assay [Lipoprotein Insulin Resistance Index (LP-IR)] was developed using HOMA-IR in 4972 nondiabetic subjects from MESA and verified independently using glucose disposal rates (GDRs) measured during hyperinsulinemic-euglycemic clamps in 56 insulin-sensitive, 46 insulin-resistant, and 46 untreated subjects with T2DM. RESULTS LP-IR exhibited stronger associations with HOMA-IR (r=0.51) and GDR (r=-0.53) than each of the individual lipoprotein parameters as well as the triglycerides/high-density lipoprotein cholesterol (TGs/HDL-C) ratio (r=0.41 and -0.44, respectively). In MESA, associations between the LP-IR score and HOMA-IR were strong in men (r=0.51), women (r=0.52), European Americans (r=0.58), African Americans (r=0.48), Chinese Americans (r=0.49), and Hispanic Americans (r=0.45). When LP-IR was categorized by HOMA-IR and either body mass index (BMI) or fasting plasma glucose (FPG), subgroups were revealed whose LP-IR scores were high (≥ 50), despite having normal BMIs (<24 kg/m(2)) or FPG (<100 mg/dL). CONCLUSIONS LP-IR scores had strong associations with multiple measures, HOMA-IR, and GDR, the former being more reflective of hepatic and the latter of peripheral insulin sensitivity, and may represent a simple means to identify individuals with IR.
Collapse
|
|
9
|
Brown N, Critchley J, Bogowicz P, Mayige M, Unwin N. Risk scores based on self-reported or available clinical data to detect undiagnosed type 2 diabetes: a systematic review. Diabetes Res Clin Pract 2012; 98:369-85. [PMID: 23010559 DOI: 10.1016/j.diabres.2012.09.005] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Revised: 06/19/2012] [Accepted: 09/04/2012] [Indexed: 01/28/2023]
Abstract
OBJECTIVE To systematically review published primary research on the development or validation of risk scores that require only self-reported or available clinical data to identify undiagnosed Type 2 Diabetes Mellitus (T2DM). METHODS A systematic literature search of Medline and EMBASE was conducted until January 2011. Studies focusing on the development or validation of risk scores to identify undiagnosed T2DM were included. Risk scores to predict future risk of T2DM were excluded. RESULTS Thirty-one studies were included; 17 developed a new risk score, 14 validated existing scores. Twenty-six studies were conducted in high-income countries. Age and measures of body mass/fat distribution were the most commonly used predictor variables. Studies developing new scores performed better than validation studies, with 11 reporting an AUC of >0.80 compared to one validation study. Fourteen validation studies reported sensitivities of <80%. The performance of scores did not differ by the number of variables included or the country setting. CONCLUSIONS There is a proliferation of newly developed risk scores using similar variables, which sometimes perform poorly upon external validation. Future research should explore the recalibration, validation and applicability of existing scores to other settings, particularly in low/middle income countries, and on the utility of scores to improve diabetes-related outcomes.
Collapse
|
|
10
|
Abstract
AIMS The current definition of impaired fasting glucose (IFG, >or=100 mg/dl) has been criticized as being too low for selective identification of individuals at risk for Type 2 diabetes. Furthermore, it is unclear whether any cut-off is justifiable from the shape of association between fasting plasma glucose (FPG) and diabetes. We therefore evaluated the association between FPG and incidence of Type 2 diabetes in a prospective, population-based study. METHODS A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort study involved 589 fasted participants in a randomly selected subcohort and 153 incident cases. Restricted cubic spline regression was used to examine non-linearity of associations and we calculated pairs of sensitivities and specificities for different cut-offs of FPG. RESULTS Spline regression with adjustment for age, sex, body mass index, waist circumference, education, physical activity, alcohol consumption, and plasma levels of triglycerides, high-density lipoprotein cholesterol and gamma-glutamyltransferase indicated that FPG was associated with risk in a non-linear fashion. Risk with higher FPG increased only above approximately 84 mg/dl. FPG>or=84 mg/dl yielded a sensitivity of 95.4% at a false-positive rate of 86.8%. In comparison, FPG>or=100 and>or=110 mg/dl yielded sensitivities of 78.4 and 42.5% and false-positive rates of 27.8 and 6.8%, respectively. The optimal cut-off of FPG was at approximately 102 mg/dl (sensitivity: 75.8%, false-positive rate: 20.7%). CONCLUSIONS Although our study suggests a threshold for increasing diabetes risk at 84 mg/dl, this cut-off would classify the vast majority of the population as at risk. The statistically optimal cut-off supports the current definition of IFG (>or=100 mg/dl).
Collapse
Affiliation(s)
- M B Schulze
- Public Health Nutrition Unit, Technische Universität München, Freising, Germany.
| | | | | | | |
Collapse
|
|
11
|
Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia 2009; 52:1714-23. [PMID: 19590846 DOI: 10.1007/s00125-009-1443-3] [Citation(s) in RCA: 155] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2009] [Accepted: 06/16/2009] [Indexed: 12/12/2022]
Abstract
Prior to the development of type 2 diabetes, glucose levels increase into the prediabetic states of isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), or combined IFG/IGT. A better understanding of the aetiology and pathophysiology of the prediabetic states might give a basis for the development of individualised prevention and treatment strategies for type 2 diabetes. Several studies have examined mechanisms and potential aetiological factors leading to the development of the different prediabetic states. The pathophysiology of i-IFG seems to include the following key defects: reduced hepatic insulin sensitivity, stationary beta cell dysfunction and/or chronic low beta cell mass, altered glucagon-like peptide-1 secretion and inappropriately elevated glucagon secretion. Conversely, the prediabetic state i-IGT is characterised by reduced peripheral insulin sensitivity, near-normal hepatic insulin sensitivity, progressive loss of beta cell function, reduced secretion of glucose-dependent insulinotropic polypeptide and inappropriately elevated glucagon secretion. Individuals developing combined IFG/IGT exhibit severe defects in both peripheral and hepatic insulin sensitivity as well as a progressive loss of beta cell function. The aetiologies of i-IFG and i-IGT also seem to differ, with i-IFG being predominantly related to genetic factors, smoking and male sex, while i-IGT is predominantly related to physical inactivity, unhealthy diet and short stature. Since the transition from the prediabetic states to overt type 2 diabetes is characterised by a non-reversible vicious cycle that includes severe deleterious effects on glucose metabolism, there are good reasons to use the well-established aetiological and pathophysiological differences in i-IFG, i-IGT and IFG/IGT to design individualised preventive strategies.
Collapse
Affiliation(s)
- K Faerch
- Steno Diabetes Center, Niels Steensens Vej 2, 2820, Gentofte, Denmark.
| | | | | | | |
Collapse
|
|
12
|
Schwartz S. Targeting the pathophysiology of type 2 diabetes: rationale for combination therapy with pioglitazone and exenatide. Curr Med Res Opin 2008; 24:3009-22. [PMID: 18828960 DOI: 10.1185/03007990802390795] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE The objectives of this article are to review the pathophysiology of type 2 diabetes mellitus (T2DM), present the rationale for a pathophysiologically based treatment approach for patients with T2DM and discuss the role of the therapeutic combination of pioglitazone and exenatide in the management of T2DM. METHODS References were identified from searches of the PubMed database that were conducted in May 2007, October 2007 and March 2008 and updates to product labeling that occurred between May 2007 and December 2007. Information was selected for inclusion on the basis of its relevance to the pathophysiology of T2DM or the clinical use of thiazolidinediones or exenatide. Discussion of other anti-diabetic treatment strategies is not included. RESULTS T2DM results from a combination of insulin resistance and beta-cell dysfunction. The combination of a thiazolidinedione and an incretin mimetic offers a combination of characteristics (e.g., glycemic control, reduced insulin resistance, decreased weight, potential cardiovascular benefits, beta-cell preservation) that addresses many of the pathophysiologic underpinnings of T2DM. A recent small placebo-controlled study assessed the effects of exenatide used with a thiazolidinedione (TZD; pioglitazone or rosiglitazone) with or without metformin. Exenatide demonstrated a greater incidence of glycosylated hemoglobin (HbA(1c)) < 7%; greater reductions in fasting blood glucose, postprandial plasma glucose and body weight; and improved beta-cell function versus the TZD/placebo group. However, exenatide was associated with a high dropout rate, and the 16-week duration of treatment in this study precluded evaluation of the long-term effects of the exenatide/pioglitazone combination. Furthermore, exenatide/pioglitazone has not been compared with any other anti-diabetic combination in a head-to-head clinical study. CONCLUSIONS Dual effects on insulin sensitivity (TZD) and insulin secretion (exenatide) make the TZD/exenatide combination a rational treatment option for patients who do not attain glycemic control with a single agent. Studies undertaken to evaluate the effects on cardiovascular outcomes and the potential for prevention of T2DM with impaired glucose tolerance may reveal additional advantages of this combination approach.
Collapse
|
|
13
|
Affiliation(s)
- Zachary T. Bloomgarden
- Zachary T. Bloomgarden, MD, is a practicing endocrinologist in New York, New York, and is affiliated with the Division of Endocrinology, Mount Sinai School of Medicine, New York, New York
| |
Collapse
|