Table 3.

Synopsis of the studies investigating the correlation of markers of acid load with insulin resistance and diabetes *.

Author	Subjects 1	Age (year)	Study Type	Variables Measured	Results	Duration/Design
Farwell et al., 2008 [69]	1496 women	>12	Cross-sectional	HCO3− Insulin resistance via both HOMA-IR and MFFM	Lower anion gap and bicarbonates correlate with increased insulin resistance	-
Mandel et al., 2012 [67]	630 (and 730 controls) (nurses)	30–55	Prospective nested case-control	HCO3− Self-Reported T2D diagnosis	Lower bicarbonates correlate with increased diabetes T2 incidence	10 years
Fagherazzi et al., 2014 [15]	66, 485 women (teachers)	mean 53	Cohort retrospective	PRAL NEAP Self-reported T2D 2	Highest PRAL-NEAP quartile shows higher incidence of diabetes T2 compared to lowest	14 years
Kiefte-de Jong et al., 2016 [14]	67,433 women 3 84,310 women 35,743 men	30–55 25–42 40–75	Cohort retrospective	PRAL NEAP A:P ratio 4 T2D	Highest PRAL-NEAP and A:P quartile shows higher incidence of diabetes T2 compared to lowest	24 years
Akter, et al., 2016 [71]	1536 men 169 women (manifacture workers)	19–69	Cross-sectional	PRAL, NEAP HOMA-IR HOMA-β HbA1c Fasting glucose	PRAL and NEAP associated with HOMA-IR 5 NEAP positively associates with HOMA-β No association with fasting glucose and HbA1c	-
Akter, et al., 2016 [70]	27,809 men 36,851 women	45–75	Cohort retrospective	PRAL, NEAP Self reported T2D diagnosis	Only PRAL associates with T2D incidence in men < 50 year-old	10 years
Xu et al., 2014 [13]	911 men	70–71	Cohort Prospective	PRAL, NEAP Insulin resistance T2D 6	No association of PRAL-NEAP with insulin sensitivity, β-cell function or diabetes incidence	18 years
Kozan et al., 2017 [72]	20 men 10 women	24–44	Placebo-controlled, crossover trial	C-peptide Insulin Fasting glucose Glucose (0–180′) GLP-1	No effect of NaHCO3 on postprandial insulin, plasma glucose, C-peptide and GLP-1 compared to placebo	0-180 min - placebo - NaHCO3 (1680 mg)
Harris et al., 2010 [73]	153 men and women 6	>50 mean 64	Randomized, placebo-controlled trial	HOMA-IR Insulin Fasting glucose	No effect of either NaHCO3 or KHCO3 on insulin, plasma glucose and HOMA-IR compared to placebo	84 days - placebo or 67.5 mmol/day of - KCl - NaHCO3 - KHCO3

* Plasma bicarbonate was included as a marker of metabolic acidosis; ¹ Healthy subjects in all studies reported, with no metabolic conditions at baseline; ² Participants were also considered diabetic if reporting elevated glucose concentration (fasting glucose ≥ 7.0 mmol/L or random glucose ≥ 11.1 mmol/L), treatment with diabetes drugs, and/or fasting glucose or HbA1c ≥ 7%. (53.0 mmol/moL); ³ Participants were all health professionals; ⁴ animal protein-to-potassium ratio; ⁵ In the stratified analyses, positive associations were confined to subjects with lower BMIs (<23 kg/m²) (P 0.03 and 0.01 for PRAL Pand NEAP, respectively); ⁶ Euglycemic–hyperinsulinemic clamp technique and the GTT to determine insulin sensitivity and β-cells function (through the calculation of IGI). Diabetes incidence was defined using fasting concentration of glucose (fasting plasma glucose ≥ 7.0 mmol/L) or the use of glucose-lowering medication; ⁷ All menopausal women.