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Hypoglycaemia, chronic kidney disease and death in type 2 diabetes: the Hong Kong diabetes registry.

Kong AP, Yang X, Luk A, Cheung KK, Ma RC, So WY, Ho CS, Chan MH, Ozaki R, Chow CC, Brown N, Chan JC - BMC Endocr Disord (2014)

Bottom Line: Yet, it remains uncertain whether hypoglycaemia-associated mortality is modified by CKD.Type 2 diabetic patients, with or without CKD at enrolment were observed between 1995 and 2007, and followed up till 2009 at hospital medical clinics.Having both risk factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91 (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p-values < 0.05).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China. jchan@cuhk.edu.hk.

ABSTRACT

Background: In patients with type 2 diabetes, chronic kidney disease (CKD) is associated with increased risk of hypoglycaemia and death. Yet, it remains uncertain whether hypoglycaemia-associated mortality is modified by CKD.

Methods: Type 2 diabetic patients, with or without CKD at enrolment were observed between 1995 and 2007, and followed up till 2009 at hospital medical clinics. We used additive interaction, estimated by relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP) to examine possible synergistic effects between CKD and severe hypoglycaemia (defined as hospitalisations due to hypoglycaemia in the 12 months prior to enrolment) on the risk of death.

Results: In this cohort of 8,767 type 2 diabetic patients [median age: 58 (interquartile range: 48 to 68) years; disease duration: 5 (1 to 11) years, men: 47.0%], 1,070 (12.2%) had died during a median follow-up period of 6.66 years (3.42-10.36) with 60,379 person-years.Upon enrolment, 209 patients had severe hypoglycaemia and 194 developed severe hypoglycaemia during follow-up (15 patients had both). In multivariable analysis and using patients without severe hypoglycaemia nor CKD as the referent group (683 deaths in 7,598 patients), severe hypoglycaemia alone (61 deaths in 272 patients) or CKD alone (267 death in 781 patients) were associated with increased risk of death [Hazard ratio, HR: 1.81(95%CI: 1.38 to 2.37) and 1.63 (1.38 to 1.93) respectively]. Having both risk factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91 (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p-values < 0.05).

Conclusions: Severe hypoglycaemia and CKD interact to increase risk of death in type 2 diabetes patients.

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Cumulative incidence of all-cause death stratified by the presence of chronic kidney disease (CKD) and severe hypoglycaemia. Legend: The model adjusted for age, sex, body mass index (BMI), smoking status, alcohol use , low-density lipoprotein cholesterol (LDL-C), high density-lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic blood pressure (SBP), HBA1c, duration of disease, and log (urinary albumin to creatinine ratio [ACR] +1), prior history of cardiovascular disease and cancer as well as drug use at enrollment, including lipid lowering drugs, renin-angiotensin system inhibitors, oral anti-diabetic drugs and insulin; P < 0.0001.
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Figure 1: Cumulative incidence of all-cause death stratified by the presence of chronic kidney disease (CKD) and severe hypoglycaemia. Legend: The model adjusted for age, sex, body mass index (BMI), smoking status, alcohol use , low-density lipoprotein cholesterol (LDL-C), high density-lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic blood pressure (SBP), HBA1c, duration of disease, and log (urinary albumin to creatinine ratio [ACR] +1), prior history of cardiovascular disease and cancer as well as drug use at enrollment, including lipid lowering drugs, renin-angiotensin system inhibitors, oral anti-diabetic drugs and insulin; P < 0.0001.

Mentions: In multivariable analysis, severe hypoglycemia predicted mortality among patients with CKD with a HR of 2.63(1.95 to 3.55) and to a lesser extent, among those without CKD [1.72(1.31 to 2.26)] (Table 2). After adjusting for confounders, CKD enhanced the HR of severe hypoglycemia for all-cause mortality from 1.81(1.38 to 2.37) to 3.91(2.93 to 5.21) (Table 3) with significant additive interaction between hypoglycemia and CKD (RERI: 1.46 (0.31 to 2.61, p = 0.0126); AP: 0.37(0.17 to 0.58, p = 0.0177) (Additional file 2: Table S2). From 1 December 1996 to 30 July 2005, 52.7% (n = 4618) of the diabetic patients have documented use of sulfonylurea and after further adjustment for the use of sulfonylurea during this period, this had little impact on the HRs.Figure 1 shows the multivariable cumulative mortality of patients categorized by hypoglycemia and CKD with the highest mortality rate in those with both CKD and hypoglycemia.


Hypoglycaemia, chronic kidney disease and death in type 2 diabetes: the Hong Kong diabetes registry.

Kong AP, Yang X, Luk A, Cheung KK, Ma RC, So WY, Ho CS, Chan MH, Ozaki R, Chow CC, Brown N, Chan JC - BMC Endocr Disord (2014)

Cumulative incidence of all-cause death stratified by the presence of chronic kidney disease (CKD) and severe hypoglycaemia. Legend: The model adjusted for age, sex, body mass index (BMI), smoking status, alcohol use , low-density lipoprotein cholesterol (LDL-C), high density-lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic blood pressure (SBP), HBA1c, duration of disease, and log (urinary albumin to creatinine ratio [ACR] +1), prior history of cardiovascular disease and cancer as well as drug use at enrollment, including lipid lowering drugs, renin-angiotensin system inhibitors, oral anti-diabetic drugs and insulin; P < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4151079&req=5

Figure 1: Cumulative incidence of all-cause death stratified by the presence of chronic kidney disease (CKD) and severe hypoglycaemia. Legend: The model adjusted for age, sex, body mass index (BMI), smoking status, alcohol use , low-density lipoprotein cholesterol (LDL-C), high density-lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic blood pressure (SBP), HBA1c, duration of disease, and log (urinary albumin to creatinine ratio [ACR] +1), prior history of cardiovascular disease and cancer as well as drug use at enrollment, including lipid lowering drugs, renin-angiotensin system inhibitors, oral anti-diabetic drugs and insulin; P < 0.0001.
Mentions: In multivariable analysis, severe hypoglycemia predicted mortality among patients with CKD with a HR of 2.63(1.95 to 3.55) and to a lesser extent, among those without CKD [1.72(1.31 to 2.26)] (Table 2). After adjusting for confounders, CKD enhanced the HR of severe hypoglycemia for all-cause mortality from 1.81(1.38 to 2.37) to 3.91(2.93 to 5.21) (Table 3) with significant additive interaction between hypoglycemia and CKD (RERI: 1.46 (0.31 to 2.61, p = 0.0126); AP: 0.37(0.17 to 0.58, p = 0.0177) (Additional file 2: Table S2). From 1 December 1996 to 30 July 2005, 52.7% (n = 4618) of the diabetic patients have documented use of sulfonylurea and after further adjustment for the use of sulfonylurea during this period, this had little impact on the HRs.Figure 1 shows the multivariable cumulative mortality of patients categorized by hypoglycemia and CKD with the highest mortality rate in those with both CKD and hypoglycemia.

Bottom Line: Yet, it remains uncertain whether hypoglycaemia-associated mortality is modified by CKD.Type 2 diabetic patients, with or without CKD at enrolment were observed between 1995 and 2007, and followed up till 2009 at hospital medical clinics.Having both risk factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91 (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p-values < 0.05).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China. jchan@cuhk.edu.hk.

ABSTRACT

Background: In patients with type 2 diabetes, chronic kidney disease (CKD) is associated with increased risk of hypoglycaemia and death. Yet, it remains uncertain whether hypoglycaemia-associated mortality is modified by CKD.

Methods: Type 2 diabetic patients, with or without CKD at enrolment were observed between 1995 and 2007, and followed up till 2009 at hospital medical clinics. We used additive interaction, estimated by relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP) to examine possible synergistic effects between CKD and severe hypoglycaemia (defined as hospitalisations due to hypoglycaemia in the 12 months prior to enrolment) on the risk of death.

Results: In this cohort of 8,767 type 2 diabetic patients [median age: 58 (interquartile range: 48 to 68) years; disease duration: 5 (1 to 11) years, men: 47.0%], 1,070 (12.2%) had died during a median follow-up period of 6.66 years (3.42-10.36) with 60,379 person-years.Upon enrolment, 209 patients had severe hypoglycaemia and 194 developed severe hypoglycaemia during follow-up (15 patients had both). In multivariable analysis and using patients without severe hypoglycaemia nor CKD as the referent group (683 deaths in 7,598 patients), severe hypoglycaemia alone (61 deaths in 272 patients) or CKD alone (267 death in 781 patients) were associated with increased risk of death [Hazard ratio, HR: 1.81(95%CI: 1.38 to 2.37) and 1.63 (1.38 to 1.93) respectively]. Having both risk factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91 (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p-values < 0.05).

Conclusions: Severe hypoglycaemia and CKD interact to increase risk of death in type 2 diabetes patients.

Show MeSH
Related in: MedlinePlus