Impact of glucose level on morbidity and mortality in elderly with diabetes and pre-diabetes

Table 1 Studies comparing cardiovascular morbidity and mortality in elderly with pre-diabetes and normal glucose tolerance

Ref.	No. of participants	Age at inclusion	Length of follow up (yr)	Population	Results
Kowall et al[9]	1466	55-74	8.8 (median)	German	Mortality rates were almost equal in the pre-diabetes and NGT groups
Schöttker et al[10]	8365	50-74	7.9 (median)	German	Major CV event1 rates were almost equal in the pre-diabetes and NGT groups
Deedwania et al[11]	4602	≥ 65	13 (median)	United States: 87% Caucasians, 13% African American	Major CV event2 rates were almost equal in the pre-diabetes and NGT groups

¹Major cardiovascular events including non-fatal stroke, non-fatal MI and cardiovascular mortality;

²Major cardiovascular events including heart failure, MI, angina pectoris, stroke and all-cause mortality. CV: Cardiovascular; NGT: Normal glucose tolerance; MI: Myocardial infarction.

Table 2 Studies comparing cardiovascular morbidity and mortality in elderly subjects with new-onset diabetes mellitus and subjects with normal glucose tolerance and long-standing diabetes mellitus

Ref.	No. of participants	Glycemic status	Age at inclusion(yr)	Length of follow up (yr)	Population	Results
Wang et al[19]	155	New-onset DM and long-standing DM	≥ 65	-	China	Microvascular complication rate was higher in long-standing DM
Selvin et al[20]	2809	New-onset DM and long-standing DM	≥ 65	-	United States	Microvascular complication rate was higher in long-standing DM
Smith et al[21]	1119	NGT and new-onset DM	≥ 65	5.9 (median)	United States	Mortality rate was higher in new-onset DM
Bethel et al[22]	59335	NGT and new-onset DM	≥ 65	10 (median)	United States	Microvascular and macrovascular complication rates were higher in new-onset-DM
Panzram et al[23]	2381	New-onset DM	All	10 (median)	German	Mortality rate was related to age of onset of DM and was higher in men
Croxson et al[24]	861	NGT, IGT, new-onset DM and long-standing DM	65-85	4.5 (median)	United Kingdom	New onset DM was associated with increased mortality
Tan et al[25]	10782	NGT and new-onset DM	≥ 65	4.6 (median)	Scotland	New onset DM was associated with increased mortality in females
Twito et al[26]	2994	New-onset DM	≥ 65	5.5 (mean)	Israel	Mortality rates in new-onset DM were associated with HbA1c levels

NGT: Normal glucose tolerance; IGT: Impaired glucose tolerance; DM: Diabetes mellitus.

Table 3 Studies on the role of tight glycemic control in long-standing diabetes mellitus

Study	No. participants	Years since diagnosis	Mean age at enrollment (yr)	Length of follow up (yr)	Population	Results
ACCORD trial[32]	10251	10 (median)	62.2 ± 6.8	3.4 (median)	United States and Canada	Terminated after 3.5 yr; excessive deaths in the intensive glycemic control arm
ADVANCE trial[33]	11140	8 (mean)	66 ± 6	5 (median)	Asia, Australasia, Europe, and North America (20 countries)	No significant effect of tight glycemic control on major macrovascular events or death; significant reduction in nephropathy incidence
VADT trial[34]	1791	11.5 (mean)	60.5 ± 9	5.6 (median)	United States military veterans; 97% males	No significant effect of tight glycemic control on major macrovascular events or death
Diabetes and aging study[36]	71092	8.3 (mean)	71 ± 7.4	3.1 (mean)	California, United States	U-shape relationship between mortality and HbA1c, with the lowest mortality rate at HbA1c 6%-8%

ACCORD: Action to Control Cardiovascular Risk in Diabetes; ADVANCE: Action in Diabetes and Vascular Disease; VADT: Veterans Affairs Diabetes Trial.

Table 4 Guideline recommendations for glycemic control in the elderly

Article	Age	HbA1c target	Population
The 2014 ADA guidelines[4]	Any age	< 7%	Adult patients without serious comorbidities
		< 8%	Patients with a more complex status (see text) Age itself not a criteria
The consensus report of the ADA and the	> 65 yr	< 7.5%	Healthy old patients
American Geriatrics Society 2012[14]		< 8%	Patients with intermediate health status (multiple chronic illnesses or 2+ instrumental impairments or mild cognitive impairment)
		< 8.5%	Patients with poor health status (end-stage chronic illnesses or moderate to severe cognitive impairment or 2+ ADL dependencies)
The 2013 IDF guidelines[39]	> 70 yr	7%-7.5%	Functionally independent old patients
		7%-8%	Functionally dependent old patients
		< 8.5%	Frail elderly or dementia
		Any HbA1c; just to avoid hypoglycemia	Patients at end-of-life

ADA: American Diabetes Association; ADL: Activities of daily living; IDF: International Diabetes Federation.