Proinsulin/insulin ratio as a predictor of insulin resistance and B-cell dysfunction in obese Egyptians ((insulin resistance &amp; B-cell dysfunction in obese Egyptians))

shabrawy, Arafa M. El; Elbana, Khaled A.; Abdelsalam, Noha

doi:10.1016/j.dsx.2019.04.044

Cited by 11 publications

(17 citation statements)

References 7 publications

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“…At enrollment, the mean weight and BMI were 93.0 ± 6.5 Kg and 32.0 ± 3.1 Kg/m2, respectively. Proinsulin/insulin ratio (0.04 ± 0.01) was lower than the values suggested to predict ß-cell exhaustion [ 21 , 22 ]. Also, the mean fasting glycaemia (93.6 ± 13.5 mg/dl) was within the normal range, and 40% of patients had impaired fasting glucose (≥100 mg/dl).…”

Section: Resultsmentioning

confidence: 91%

“…Large population studies with a duration of up to 27 years reported increased serum proinsulin levels as predictors of T2DM development within 2–7 years [ 27 , 34 – 36 ]. More recently, the cutoff value of proinsulin ≥7.829 pmol/l has been reported to be a predictor of β-cell dysfunction with a sensitivity of 95.8% and a specificity of 72.2% in a cohort of obese adolescents [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Patients with signs or symptoms suggestive of T deficiency underwent to TT measurement. Those with hypogonadism (TT < 264 ng/dl confirmed by at least two measurements of serum TT [ 22 ]) willing to undergo to VLCKD were recruited in this study.…”

Section: Subject and Methodsmentioning

confidence: 99%

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The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study

et al. 2020

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Background Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear. Aim To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism. Methods Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks. Results Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment. Conclusions This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism.

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Section: Resultsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study

et al. 2020

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“…In contrast to our results, two recent cross-sectional studies found a positive association of PIR with HOMA-IR in diabetic participants 31 and in obese Egyptians. 32 However, these results were not corrected for possible confounders. Apart from the direct association with elevated fasting glucose and the inverse association with an elevated waist circumference, PIR was not related to the other components of the metabolic syndrome, namely elevated triglycerides, reduced HDL cholesterol and elevated blood pressure, which is in line with a study by Pivatto et al showing that proinsulin and insulin alone, but not PIR, were associated with the metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

Then

Gar

Thorand

et al. 2020

BMJ Open Diab Res Care

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IntroductionWe investigated the association of the proinsulin to insulin ratio (PIR) with prevalent and incident type 2 diabetes (T2D), components of the metabolic syndrome, and renal and cardiovascular outcomes in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006–2008)/FF4 study (2013–2014).Research design and methodsThe analyses included 1514 participants of the KORA F4 study at baseline and 1132 participants of the KORA FF4 study after a median follow-up time of 6.6 years. All-cause and cardiovascular mortality as well as cardiovascular events were analyzed after a median time of 9.1 and 8.6 years, respectively. The association of PIR with T2D, renal and cardiovascular characteristics and mortality were assessed using logistic regression models. Linear regression analyses were used to assess the association of PIR with components of the metabolic syndrome.ResultsAfter adjustment for sex, age, body mass index (BMI), and physical activity, PIR was associated with prevalent (OR: 2.24; 95% CI 1.81 to 2.77; p<0.001) and incident T2D (OR: 1.66; 95% CI 1.26 to 2.17; p<0.001). PIR was associated with fasting glucose (β per SD: 0.11±0.02; p<0.001) and HbA1c (β: 0.21±0.02; p<0.001). However, PIR was not positively associated with other components of the metabolic syndrome and was even inversely associated with waist circumference (β: −0.22±0.03; p<0.001), BMI (β: −0.11±0.03; p<0.001) and homeostatic model assessment of insulin resistance (β: −0.22±0.02; p<0.001). PIR was not significantly associated with the intima-media thickness (IMT), decline of kidney function, incident albuminuria, myocardial infarction, stroke, cardiovascular or all-cause mortality.ConclusionsIn the KORA F4/FF4 cohort, PIR was positively associated with prevalent and incident T2D, but inversely associated with waist circumference, BMI and insulin resistance, suggesting that PIR might serve as a biomarker for T2D risk independently of the metabolic syndrome, but not for microvascular or macrovascular complications.

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“…27 Elevated proinsulin and proinsulin/insulin ratio were interpreted as an indication of early subclinical β-cell dysfunction, especially insulin secretory defects. 28 This study was a single-centre study, with the possibility of selection bias. And the relatively small sample size of this study may be insufficient to make conclusive statements.…”

Section: Discussionmentioning

confidence: 99%

Heterozygous PAX6 mutations may lead to hyper‐proinsulinaemia and glucose intolerance: A case–control study in families with congenital aniridia

et al. 2020

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Aim PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case–control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA. Methods In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age‐matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated. Results Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032). Conclusion PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients.

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Proinsulin/insulin ratio as a predictor of insulin resistance and B-cell dysfunction in obese Egyptians ((insulin resistance & B-cell dysfunction in obese Egyptians))

Cited by 11 publications

References 7 publications

The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study

The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study

Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

Heterozygous PAX6 mutations may lead to hyper‐proinsulinaemia and glucose intolerance: A case–control study in families with congenital aniridia

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