Type 2 Diabetes: When Does It Start?

Sagesaka, Hiroyuki; Sato, Yuka; Someya, Yuki; Tamura, Yasuaki; Shimodaira, Masanori; Miyakoshi, Takahiro; Hirabayashi, Kazuko; Koike, Hideo; Yamashita, Koh; Watada, Hirotaka; Aizawa, Toru

doi:10.1210/js.2018-00071

Cited by 43 publications

(33 citation statements)

References 20 publications

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“…Since diabetes is not usually diagnosed until several years after the appearance of insulin and glucose deregulation, it is crucial to detect the early stages of the disease through the use of adequate biomarkers of reduced insulin sensitivity [23]. In this context, studies conducted in non-diabetic subjects are useful in evaluating novel biomarkers to identify the susceptibility to develop T2D through the evaluation of intermediate phenotypes such as the insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

Arpón

Santos

Milagro

et al. 2019

IJMS

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Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or insulin action. Since few studies have addressed the relation between DNA methylation patterns with elaborated surrogates of insulin secretion/sensitivity based on the intravenous glucose tolerance test (IVGTT), the aim of this study was to evaluate the association between DNA methylation and an insulin sensitivity index based on IVGTT (calculated insulin sensitivity index (CSi)) in peripheral white blood cells from 57 non-diabetic female volunteers. The CSi and acute insulin response (AIR) indexes, as well as the disposition index (DI = CSi × AIR), were estimated from abbreviated IVGTT in 49 apparently healthy Chilean women. Methylation levels were assessed using the Illumina Infinium Human Methylation 450k BeadChip. After a statistical probe filtering, the two top CpGs whose methylation was associated with CSi were cg04615668 and cg07263235, located in the catenin delta 2 (CTNND2) and lipoprotein lipase (LPL) genes, respectively. Both CpGs conjointly predicted insulin sensitivity status with an area under the curve of 0.90. Additionally, cg04615668 correlated with homeostasis model assessment insulin-sensitivity (HOMA-S) and AIR, whereas cg07263235 was associated with plasma creatinine and DI. These results add further insights into the epigenetic regulation of insulin sensitivity and associated complications, pointing the CTNND2 and LPL genes as potential underlying epigenetic biomarkers for future risk of insulin-related diseases.

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Section: Introductionmentioning

confidence: 99%

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

Arpón

Santos

Milagro

et al. 2019

IJMS

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“…It is unclear in the literature whether there is evidence of insulin resistance or renal lipotoxicity, or its surrogates (dyslipidaemia or high BMI) at this point, and we have discussed the risk of under-ascertainment of MetS components earlier. Interestingly, Sagesaka et al demonstrated that type 2 diabetes could be predicted up to 10 years before the patient developed the condition using the same factors used to diagnose metabolic syndrome [ 30 ]. Unfortunately, they did not examine if the components of MetS rose and fell, respectively, as fasting plasma glucose did.…”

Section: Discussionmentioning

confidence: 99%

Risk of Metabolic Syndrome in Kidney Stone Formers: A Comparative Cohort Study with a Median Follow-Up of 19 Years

Geraghty

Cook

Roderick

et al. 2021

JCM

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Background: Kidney stone formers (SF) are more likely to develop diabetes mellitus (DM), but there is no study examining risk of metabolic syndrome (MetS) in this population. We aimed to describe the risk of MetS in SF compared to non-SF. Methods and Materials: SF referred to a tertiary referral metabolic centre in Southern England from 1990 to 2007, comparator patients were age, sex, and period (first stone) matched with 3:1 ratio from the same primary care database. SF with no documentation or previous MetS were excluded. Ethical approval was obtained and MetS was defined using the modified Association of American Clinical Endocrinologists (AACE) criteria. Analysis with cox proportional hazard regression. Results: In total, 828 SF were included after 1000 records were screened for inclusion, with 2484 age and sex matched non-SF comparators. Median follow-up was 19 years (interquartile range—IQR: 15–22) for both stone formers and stone-free comparators. SF were at significantly increased risk of developing MetS (hazard ratio—HR: 1.77; 95% confidence interval—CI: 1.55–2.03, p < 0.001). This effect was robust to adjustment for pre-existing components (HR: 1.91; 95% CI: 1.66–2.19, p < 0.001). Conclusions: Kidney stone formers are at increased risk of developing metabolic syndrome. Given the pathophysiological mechanism, the stone is likely a ‘symptom’ of an underlying metabolic abnormality, whether covert or overt. This has implications the risk of further stone events and cardiovascular disease.

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“…The majority of facilities in our survey did not screen for diabetes until there were symptoms of diabetes or complications of diabetes, both later stages of the disease attributed with greater morbidity from previous months to years of asymptomatic hyperglycemia. Diabetes diagnosis typically occurs late in the disease progression -there is an average of 10 years where a patient has elevated blood sugars prior to a diagnosis [24]. When caught earlier, diabetes is more easily managed and a great amount of damage to the vascular and immune systems can be avoided.…”

Section: Discussionmentioning

confidence: 99%

Examination of Mortality Due to Diabetes and Assessment of Diabetes-Related Healthcare Services in Rural Western Kenya

Purdy

Sifuna

Otieno

et al. 2020

Preprint

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BackgroundThe prevalence of diabetes is increasing in low-and middle- income countries, due to the adoption of a western diet and decreased physical activity. Diabetes is often underdiagnosed, and the management of the disease is resource intensive. In this paper, we examine the burden of diabetes on a rural population in western, Kenya and assess the ability of the health care system to diagnose, manage, and treat diabetes. MethodsWe utilized verbal autopsies from the Kombewa Health and Demographic Surveillance Site in rural western Kenya from 2011-2018 to measure the burden of diabetes among the deceased. We classified deaths as either primarily caused by diabetes according to verbal autopsy or as a death of any cause that reported having a previous diagnosis of diabetes. We also conducted a survey of health facilities to measure the capacity of the health system to prevent, diagnose, and manage diabetes.ResultsFrom 2011-2018, 85 people died with diabetes as the verbal autopsy reported primary cause in the region (1.8% of verbal autopsies). An additional 4.6% of verbal autopsies indicated the deceased had a previous known diagnosis of diabetes. Deaths with diabetes as the primary cause of death increased with age and were more likely among men than women. Of the 23 surveyed health facilities, 26% regularly screened for diabetes and 39% managed diabetes in their patients. We found a lack of screening and resources to consistently treat patients with diabetes. All facilities reported not having the full range of medications indicated by the Kenya Essential Medication List to treat diabetes. ConclusionsOur results suggest that the undetected burden of diabetes may be greater in rural Western Kenya than previous country-wide studies suggested. Additionally, our results demonstrate that most health facilities in the region do not have the capacity to screen for diabetes nor do they have stocks of the medications to treat diabetes. This lack of care results in patients being referred to larger hospitals for treatment. As the prevalence of diabetes increases in Kenya, and other low- and middle-income countries, improved detection and treatment of diabetes will be important to limiting the deleterious chronic damage caused by undiagnosed and uncontrolled diabetes.

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Type 2 Diabetes: When Does It Start?

Cited by 43 publications

References 20 publications

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

Risk of Metabolic Syndrome in Kidney Stone Formers: A Comparative Cohort Study with a Median Follow-Up of 19 Years

Examination of Mortality Due to Diabetes and Assessment of Diabetes-Related Healthcare Services in Rural Western Kenya

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