|Year : 2022 | Volume
| Issue : 4 | Page : 177-182
Prevalence of risk factors for diabetes in adult offspring of type 2 diabetes mellitus patients
Ruchika Saini1, Monica Gupta1, Shivani Jaswal2, Sarabmeet Singh Lehl1, Gautam Jesrani1, Samiksha Gupta1
1 Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
2 Department of Biochemistry, Government Medical College and Hospital, Chandigarh, India
|Date of Submission||15-Nov-2022|
|Date of Decision||29-Nov-2022|
|Date of Acceptance||09-Dec-2022|
|Date of Web Publication||07-Jan-2023|
Department of General Medicine, Level-4, D-Block, Government Medical College and Hospital, Sector-32, Chandigarh - 160 030
Source of Support: None, Conflict of Interest: None
Background: The risk of developing type 2 diabetes mellitus (T2DM) and associated metabolic abnormalities is higher in adult offspring of patients with T2DM. Various genetic and environmental influences play a facilitatory role. These determinants can lead to the early onset of hyperglycemia, unrecognized end-organ changes, and cardiovascular morbidity.
Objective: The objective of this study was to identify the presence of undiagnosed diabetes and prediabetes in the otherwise healthy adult offspring of patients with T2DM and to study early metabolic abnormalities among these individuals.
Materials and Methods: The study population consisted of 100 healthy offspring aged 18 years and above, of parents with T2DM, enrolled from the medicine outpatient area. Anthropometric characteristics, routine investigations and diabetes defining parameters, fasting plasma insulin, and homeostatic model assessment-estimated insulin resistance (HOMA-IR) were assessed.
Results: The age and body mass index of participants were 32.30 ± 9.33 years and 25.08 ± 4.58 kg/m2, respectively. About 33.3% of males and 76.4% of females had abnormal waist circumference and metabolic syndrome was found in 26% of the offspring. Twenty-eight participants displayed dysglycemia, of which 10 were diagnosed with prediabetes and 18 with diabetes. C-reactive protein, total cholesterol, triglyceride values, apolipoprotein A, B, and their ratio, and HOMA-IR were significantly raised, and high-density lipoprotein was found significantly low in patients with this newly diagnosed T2DM.
Conclusion: A significant number of asymptomatic offspring of patients with T2DM have incipient diabetes and prediabetes status, which is unidentified. Further, metabolic parameters are more deranged in those with newly diagnosed diabetes and prediabetes. Therefore, opportunistic screening for these offspring should be done routinely.
Keywords: Adult offspring, homeostatic model assessment-estimated insulin resistance, metabolic syndrome, type 2 diabetes mellitus
|How to cite this article:|
Saini R, Gupta M, Jaswal S, Lehl SS, Jesrani G, Gupta S. Prevalence of risk factors for diabetes in adult offspring of type 2 diabetes mellitus patients. Int J Non-Commun Dis 2022;7:177-82
|How to cite this URL:|
Saini R, Gupta M, Jaswal S, Lehl SS, Jesrani G, Gupta S. Prevalence of risk factors for diabetes in adult offspring of type 2 diabetes mellitus patients. Int J Non-Commun Dis [serial online] 2022 [cited 2023 Feb 1];7:177-82. Available from: https://www.ijncd.org/text.asp?2022/7/4/177/367309
| Introduction|| |
Type 2 diabetes mellitus (T2DM) is a heterogeneous disease having a strong genetic association. There is a 3.5-fold increased risk of getting diabetes if a single parent is affected and this risk increases up to 6-fold if both parents are affected. The concordance rate of incidence of T2DM in monozygotic and dizygotic twins is 60% and 20%–30%, respectively.
Having a parental history of T2DM not only predisposes an individual to an early onset of diabetes but also the cluster of metabolic abnormalities known as metabolic syndrome (MetS). The first-degree relatives of patients with T2DM have an early onset of disease and are more inclined to obesity. Offspring of parents with T2DM in India are especially at high risk for the development of T2DM early in life considering their family predisposition, ethnicity, and unhealthy lifestyle. Earlier studies from India have shown that, even in healthy offspring of patients with T2DM parents, abnormalities of insulin secretion, as well as insulin resistance (IR), could be present. Belonging to Asian ethnicity is another risk factor for developing diabetes as Asian Indians are more prone to accumulate higher hepatic fat leading to greater IR.
Evaluating diabetes in offspring of T2DM patients provides insight into the parental transmission of diabetes and variable contribution by maternal and paternal genetic makeup. Various genome-wide association studies have identified more than 50 genetic variants but these variants only explain <10% of the observed heritability. This variability could be explained by environmental factors and the adoption of the same unhealthy habits as of parents. Prevention at an initial stage is the key to halt this lifestyle-based disease. Nishigaki et al. have shown in their research that only 50% of offspring were aware of their risk and engaged in different preventive behavior. This emphasizes the need for screening of risk factors in our population and close monitoring for the development of diabetes, prediabetes, MetS, and cardiometabolic parameters, especially in groups that are at the highest risk of developing the disease.
The objective of this study was to identify the presence of undiagnosed diabetes and prediabetes in the otherwise healthy adult offspring of patients with T2DM and to study early metabolic abnormalities among these individuals.
| Materials and Methods|| |
Design and study population
A cross-sectional study was conducted at our teaching hospital from January 2020 to December 2021. Patients with T2DM visiting the outpatient area were asked about their offspring's glycemic status. Adult offspring of these diabetic parents were contacted and explained about the study and its implications in their vernacular language. Written informed consent was obtained from all participants. Those with age <18 years, diagnosed with T1DM or with any severe illness such as acute infections, autoimmune disease, and on steroidal medications were excluded.
Ethical approval and consent to participate
The study was approved by the institutional ethics committee (Letter no. GMC/IEC/2019/200, Date: December 18, 2019). Individuals providing written informed consent were included for further assessment, and study participants were assured that the confidentiality of their personal data would be maintained.
The principal investigator collected detailed demographic information, followed by complete anthropometry and detailed physical examination. An early morning blood sample was taken after fasting of 8 h for investigations which included fasting plasma glucose, postprandial glucose, glycosylated hemoglobin (HbA1c), lipid profile, apolipoprotein (Apo) A1, Apo B, plasma insulin, and C-reactive protein (CRP). Homeostatic model assessment (HOMA) was used for assessing IR and beta-cell function.
Data were exported into Microsoft® Excel workbook 2019 and exported into SPSS version 26.0 (IBM, USA). Categorical variables were expressed as numbers (n) and percentages (%) and compared using the Chi-square test. Quantitative data were expressed as mean and standard deviation (SD) and compared using an independent t-test between the two groups. P < 0.05 was considered statistically significant.
| Results|| |
Description of the study population
A total of 100 adult offspring of patients with T2DM were taken into consideration. Basic laboratory parameters are depicted in [Table 1]. Total cholesterol (TC) and triglycerides (TG) were significantly higher in males; however, high-density lipoprotein (HDL), Apo A1, and B levels were quite similar in the male and female populations. Overall male participants had more deranged metabolic characteristics compared to female participants. The study population was classified into normoglycemic, prediabetes, and diabetes based on HbA1c levels. Dysglycemia was present in 28% of offspring. Out of these 28 dysglycemic participants, 10 and 18 were found to have prediabetes and diabetes, respectively. Data are depicted in [Table 1] and [Figure 1]. The prevalence of dysglycemia was 30.3% and 23.5% in males and females, respectively. In a comparison of the prevalence of dysglycemia across age groups, it was significantly higher in ≥30 years group (42.2%) compared to <30 years group (16.4%).
|Table 1: Anthropometric and laboratory variables of the study population|
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Normoglycemic and individuals with prediabetes did not show significantly different anthropometric characteristics. Newly diagnosed patients with T2DM had significantly higher weight, waist circumference (WC), body mass index (BMI), platelet count, urea, creatinine, TC, TG, Apo A1 and Apo B, CRP, and plasma insulin levels in comparison to normoglycemic as shown in [Table 2]. Furthermore, patients with T2DM participants had significantly lower HDL levels than normal participants. Laboratory characteristics did not differ significantly between prediabetes and normoglycemic participants. The prevalence of MetS was 15.3% among healthy controls, 40% among patients with prediabetes, and 61.1% among patients with T2DMs. In comparison with normoglycemic and participants with prediabetes, patients with T2DMs had significantly higher HOMA-estimated IR (HOMA-IR) [Figure 2]. However, no significant difference was seen between normoglycemic and participants with prediabetes.
|Figure 2: Distribution of HOMA-IR among offspring with prediabetes and newly diagnosed diabetes. HOMA-IR: Homeostatic model assessment-estimated insulin resistance|
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|Table 2: Anthropometric and laboratory characteristics among offspring with prediabetes and diabetes|
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| Discussion|| |
Based on HbA1c levels as per the american diabetes association (ADA) criteria 2019, 28% of the offspring of patients with T2DM displayed abnormal plasma glucose and we could establish a prevalence of prediabetes in 10% and T2DM in 18%. These figures are considerably higher than the prevalence of diabetes (9.6%) and prediabetes (7.8%) in the Indian population aged 20–79 years. Our results were analogous to a study from a rural region of Madhya Pradesh which reported a prevalence of prediabetes and diabetes at 14.5% and 10%, respectively. Similarly, a study in Catalonia by Costa et al. illustrated an abnormal glucose tolerance in more than 30% of the progeny of patients with T2DM. Kumar et al. in the North Indian population of 172 first-degree relatives of patients with T2DM, illustrated the prevalence of impaired fasting glucose in 37% and diabetes in 11.05%. This prevalence rate is higher than ours probably because they performed an oral glucose tolerance test (OGTT) to detect glucose intolerance. These studies strongly advocate that people with a family history of T2DM deserve special targeted medical attention to expeditiously detect and prevent forthcoming dysglycemia.
The mean (±SD) age of the study population was 32.30 (±9.33) years, it is a crucial time period before the onset of T2DM where primary intervention can halt the onset and progression of diabetes and even reverse diabetes. We know that the pathological changes appear at a premature stage in these high-risk individuals as compared to the general population, necessitating early screening of these high-risk individuals. Sixty percent of participants had a BMI above the normal range and around 33.3% of male and 76.4% of female participants had WC above normal for the Asian population. The presence of positive family history along with increased BMI doubled the risk of getting the disease. The geographical variation in the prevalence of obesity across the region mirrors the prevalence of diabetes. In the United States and Europe, a meta-analysis of prospective cohort studies illustrated that obese men had a 7-fold higher risk of developing T2DM and obese women had a 12-fold higher risk when compared with individuals having weight in the normal range. In a Korean genome and epidemiology study, Jeon et al. studied WC trajectories and established that the association between weight gain and T2DM risk depends on the changes in abdominal obesity status.
Increased platelet count and mean platelet volume as in our dysglycemic offspring are indicators of thrombotic potential and are considered risk factors for microvascular complications in patients with T2DMs. Akinsegun et al. and several other authors in their research have found significantly higher platelet count in a first-degree relative of patients with T2DM than in controls without a family history. Raised CRP in dysglycemic individuals reflects low-grade inflammation which can foresee the likelihood of developing cardiovascular events both in patients with T2DM and nondiabetic populations and IR. The atherogenic lipid profile of patients with T2DM participants is also a matter of concern. Velu et al. depicted significantly higher serum levels of TG and TC in a normoglycemic first-degree relative of patients with T2DM than controls. The existence of dyslipidemia in the progeny of patients with T2DM is considered a predictor for the early development of macrovascular complications. A cohort study conducted over 16 years among 1228 prediabetic participants having a positive family history demonstrated that participants with deranged lipids had a higher tendency to progress to diabetes. ApoB/ApoA ratio was found significantly higher in our patients with T2DM than in normal participants. Similarly, Sheriff et al. also reported that this ratio was notably associated with the severity of coronary artery disease in patients of T2DM. AMORIS study, along with other epidemiological studies proclaimed that the ratio of ApoB/A1 can be superior in predicting the risk of cardiovascular disease (CVD) than traditional lipid markers such as cholesterol, low-density lipoprotein, and HDL.
MetS was present in 26% of participants as per the International Diabetes Federation criteria. A prospective open cohort study comprised 1766 normoglycemic first-degree relatives of patients with T2DM were followed for 15 years and it was discovered that those who developed T2DM at end of the study had a higher MetS Z-score at baseline. These findings validate that presence of MetS is associated with a greater risk of developing T2DM. The prevalence of dysglycemia (28%) and MetS (26%) was parallel in our study suggesting that MetS and T2DM are closely related diseases and driven by the same metabolic disturbances.
We found significantly higher plasma insulin and HOMA-IR in patients with T2DM than in normoglycemic and prediabetic participants. Velu et al. conducted a study in a nondiabetic first-degree relative of patients with T2DM patients and revealed that despite having normal plasma glucose they had significantly higher IR and fasting plasma insulin. Costa et al. in their study showed that basal insulin level was higher in first-degree relatives of patients with T2DM. Similarly, Kumar et al. also showed a significantly higher level of plasma insulin in a first-degree relative of patients with T2DM. Results of our study and previous studies concluded that there was a high prevalence of IR and fasting plasma insulin in the progeny of patients with T2DM even in normoglycemic individuals. It was witnessed that IR rises progressively from normoglycemic to diseased state. Hence, a prerequisite to evaluate IR since it is an underlying mechanism and predictor of CVD, diabetes, hypertension, obesity, and other consequence of MetS and impaired insulin sensitivity.
This study was constrained by the COVID-19 pandemic, resulting in a small sample size. OGTT was not carried out and IR was measured by HOMA-IR indices at our center due to feasibility issues during the COVID-19 pandemic. We are aware that the hyperinsulinemic-euglycemic clamp and intravenous glucose tolerance test are the most reliable and reference standard for IR.
| Conclusion|| |
Based on our data, most of the risk of T2DM is associated with a positive family history which in turn is mediated through several variables such as obesity, deranged lipid profile, and IR. A significant number of offspring of patients with T2DM patients were having incipient diabetes and prediabetes status, which was unidentified and asymptomatic. Further, metabolic parameters were more deranged in newly diagnosed offspring with T2DM and prediabetes. The finding of the study supports the importance of regular screening for diabetes, prediabetes, and other cardiovascular threats in the offspring of patients with T2DM together with primary care programs, involving intervention at the family and community level.
Ethical approval statement
The study was approved by the institutional ethics committee (Letter no. GMC/IEC/2019/200, Date: December 18, 2019).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]