Our study suggested that TC/HDL-C, AIP, LDL-C/HDL-C and non-HDL-C/HDL-C were positively correlated with the risk of diabetes in the Chinese population with H-type hypertension. In addition, this study for the first time revealed that AIP had relatively superior ability to assessing the risk of prevalent diabetes, compared to TC/HDL-C, LDL-C/HDL-C and non-HDL-C/HDL-C.
Previous studies on the relationship between AIP and diabetes are limited. A prospective study involving 2676 middle-aged Turkish people found that after adjusted for multivariate, AIP predicted diabetes significantly with RRs of 1.48 (95% CI:1.22-1.80) in men and 1.32 (95% CI:1.06-1.64) in women for per 1 SD increment.  Similarly, a meta-analysis indicated that the standard mean difference (SMD) in AIP for patients with or without diabetes was 1.78 (95%CI: 1.04–2.52). In accordance with the above results, our study showed that the risk of diabetes increased by 1.84 times for per 1SD increment (OR=2.84, 95%CI:2.37-3.41; P＜0.001).
In addition, our study found that TC/HDL-C and LDL-C/HDL were positively correlated for the risk of diabetes in the Chinese population with H-type hypertension, and there was no statistical difference in their ability of identifying diabetes. TC/HDL-C can indirectly estimate of LDL-C particle number and can be a strong predictor of the risk of atherosclerosis and coronary heart disease. Similar to the findings of our study, A cross-sectional study involving 935 Chinese hypertensive patients showed that LDL-C/HDL-C was significantly associated with the onset of diabetes. Compared with the lower tertile, the risk of diabetes was 1.6 times in the upper tertile. Ming Zhang et al. followed up 11929 non-diabetic patients for 6 years and found that TC/HDL-C was associated with diabetes risk (HR=1.66, 95%CI: 1.23-2.25). In addition, the study also revealed interactions between TC/HDL- C with age and BMI. However, a prospective study conducted in Isfahan found that TC/HDL-C was not significantly correlated to risk of diabetes. The above results are inconsistent with our study, which may be caused by the following reasons: 1) the race of the population included in the study is different; 2) the population of H-type hypertension was included in this study; 3) current study adjusted for more confounding factors.
Non-HDL-C was introduced as an novel means to refine risk estimation beyond LDL-C from Friedewald's formula in the presence of elevated triglyceride levels (≥200 mg/dl), since associated changes of the VLDL-TG/VLDL-C ratio may lead to LDL-C undercalculation. our study provided a novel insight that non-HDL-C/HDL-C was positively correlated to diabetes among H-type hypertension populations in China. In accordance with the results of current study, Minghui Han et al. conducted a 6-year follow-up of 11487 non-diabetic Chinese populations and found that the baseline non-HDL-C/HDL-C, an absolute gain in non-HDL-C/HDL-C and a relative gain in non-HDL-C/HDL-C was associated with the risk of diabetes. Compared with quartile1 group, the ORs of diabetes in the quartile4 group were 2.16 (95%CI: 1.62–2.88) ,2.00 (95%CI: 1.52–2.61) and 1.97 (95%CI: 1.49-2.60), respectively. Minghui Han et al. performed a retrospective study on 41,821 Korean adults who participated in routine health screening examinations and found that elevated non-HDL-C/HDL-C was significantly associated with odds of incident diabetes (OR=1.54, 95%CI: 1.48-1.60 in man ; OR=1.84,95%1.77-1.91 in women).
The specific mechanism of the association between lipid ratios and diabetes is currently unclear. However, Previous studies had proposed some possible mechanisms regarding the relationship between blood lipids and diabetes. As we all knew, blood glucose homeostasis was maintained by the balanced interaction between insulin action and insulin secretion. When the feedback loop between the action of insulin and insulin secretion is not functioning properly, it would lead to abnormal blood glucose levels and even diabetes. Some epidemiological studies have demonstrated that lipid ratios are independent risk factor for insulin resistance. For example, a cross-sectional study from a Czech population revealed that AIP was significantly associated with insulin resistance (OR=1.32; 95%CI: 1.09-1.61). In addition, Tingting Du et al. analyzed the data from the China Health Nutrition Survey 2009 and found that after adjusting for multivariate, TC/HDL-C, LDL-C/HDL and non-HDL/HDL-C were all correlated to insulin resistance. When treating quartile 1 group as reference group, the adjusted ORs of insulin resistance in quartile4 group were 2.31 (95%CI: 1.84-2.89), 1.71 (95%CI1.38-2.12) and 2.31 (95%1.84-2.89), respectively. The association between lipid ratios and β cell function was also documented in previous literature. Recently, a prospective study involving 1246 Hispanics and African Americans indicated that a higher TG/HDL-C ratio was associated with impaired β-cell function. Sabine Ru¨tti et al. conducted an experiment in vitro and found that LDL-C/HDL-C can modulated the function and apoptosis of human and murine β cells. Also, increased non-HDL-C/HDL-C ratio might be associated with β-cell dysfunction. The underlying molecular mechanisms explaining the link between lipids and diabetes are not understood in depth. Currently, the most widely accepted view is lipotoxicity comprising endoplasmic reticulum pressure, mitochondrial dysfunction, oxidative stress and inflammation, which can induce insulin resistance and affect β-cell function.[45, 46] besides, Chie Ebato et al. found that dyslipidemia can inhibit β-cell insulin secretion and proliferation by affecting the autophagy ability of β-cells. Low plasma level of HDL-C is an independent risk factor for atherosclerosis and may also contribute to the pathophysiology of diabetes. The possible mechanism is that low levels of HDL-C may inhibit insulin secretion, impair insulin sensitivity and impair glucose uptake of muscle via AMP-activated protein kinase. Although current research has initially explored the molecular mechanisms of lipids and diabetes, there are still controversies. We need further basic research to clarify the relationship between blood lipids and diabetes.
Some limitations and strengths of the current study need to be mentioned when interpreting our findings. Our study evaluated the association between different lipid ratios (TC/HDL-C, AIP, LDL-C/HDL-C, and non-HDL-C/HDL-C) and the risk of diabetes among the Chinese population with H-type hypertension for the first time. Compared with other lipid ratios, AIP is superior in terms of assessing the relationship between lipid ratios and diabetes. nevertheless, several limitations of this study need to be pointed out. First, this study is a cross-sectional study that cannot explain the causal relationship between lipid ratio and diabetes. Second, our study used fasting plasma glucose as the criterion for diagnosing diabetes, and did not detect glycosylated hemoglobin and performed oral glucose tolerance tests. Therefore, some diabetic patients might miss the diagnosis. This may lead to underestimation of the relationship between blood lipid ratio and diabetes. However, the same method of diagnosing diabetes by measuring fasting blood glucose was used in the Framingham Heart Study. Third, present study recruited H-type hypertension population in southern China, so it cannot be generalized to other groups.
In conclusion, we found that all of lipid ratios (TC/HDL-C, AIP, LDL-C/HDL-C, and non-HDL-C/HDL-C) in the Chinese population with H-type hypertension were independently and positively correlated with the risk of prevalent diabetes. Also, AIP seemed to perform better in assessing the correlation between lipid ratios and diabetes. This suggests that early monitoring of AIP for Chinese patients with H-type hypertension and dyslipidemia, while early intervention may reduce the risk of diabetes.