Metabolic disorders in prediabetes: From mechanisms to therapeutic management

Table 1 American Diabetes Association diagnostic criteria

Indicator	Numerical range	Ref.
FBG	100-125 mg/dL (5.6-6.9 mmol/L)	[8-11]
IGT	140-199 mg/dL (7.8-11.0 mmol/L)
A1C	5.7%-6.4% (39-47 mmol/mol/L)

FBG: Fasting blood glucose; IGT: Impaired glucose tolerance value; A1C: Glycated hemoglobin.

Table 2 Prevalence of prediabetes in China (2008–2018)

Yr	Prevalence in males	Prevalence in female	Total prevalence	Ref.
2008	16.1%	14.9%	15.5%	Wang et al[14]
2013	36.4%	35%	35.7%	Wang et al[14]
2015-2017	–	–	35.2%	Wang et al[15]
2018	–	–	38.1%	Li et al[16]

Table 3 Main intervention modalities for prediabetes

Intervention method	Cycle time, follow-up time	Effect	Ref.
Lifestyle intervention	4 months, 1 yr follow up	Blood glucose and lipids can be effectively controlled	Gokulakrishnan et al[28]
Lifestyle intervention	1 yr	Effective reduction of disease risk in patients with prediabetes	Hu et al[29]
Lifestyle intervention	1 yr	Weight loss 34.1% higher than in the diatomic group	Apolzan et al[30]
Metformin	10 yr	Enhanced glycemic control to improve health outcomes	Jonas et al[31]
Metformin	1 yr	More effective in body weight reduction. Better results than life interventions	O’Brien et al[32]
Metformin	5 yr	Weight loss 2.5% higher than life intervention group	Apolzan et al[30]
Metformin	15 yr	Compared with the placebo group, 17% lower incidence of diabetes	Diabetes Prevention Program Research Group[33]
GLP-1 receptor agonist	3 yr	Significant weight loss and improved blood sugar	le Roux et al[34]
GLP-1 receptor agonist	17 months	Significant weight loss	Wilding et al[35]
GLP-1 receptor agonist	14 wk	Significant reduction of body weight and improved relevant glucose tolerance indicators	Kim et al[36]

GLP-1: Glucagon-like peptide-1.

Table 4 Dosage schedule for metformin for treating patients with prediabetes

Trial population	Prescribed dosage	Associated or not	Treatment cycle	Reversal rate	Ref.
Adolescents	1000 mg/d	Rosiglitazone (2 mg)	3.9 yr	80% improvement in glucose tolerance	Zinman et al[137]
Adolescents	1000 mg/d	No	6 months	45% increase in insulin sensitivity	Srinivasan et al[138]
Adults	850 mg/d	No	1 yr	7% reduction in the incidence of diabetes	Andreadis et al[139]
Adults	2000 mg/d	No	1 yr	Increased insulin sensitivity (P < 0.01)	Malin et al[134]
Adults	1500-2000 mg/d	Exenatide (10-20 μg/d)	1 yr	64% improvement in prediabetes remission rates	Tao et al[140]

Table 5 Types of Glucagon-like peptide-1 receptor agonists currently approved for marketing in China and their recommended clinical dosage

Name	Molecular formula	Number of amino acids	Recommended initial dosage	Recommended dosage for prediabetes	Ref.
Exenatide	C149H234N40O47S	39	10 μg/day	10-20 μg/day	Tavlo et al[51]
Liraglutide	C172H265N43O51	9	0.6-1.2 mg/day	3 mg/day	le Roux et al[34]
Dulaglutide	C40H50N8O5	8	0.75 mg/week	–	–
Lixisenatide	C215H347N61O65S	44	10 μg/day	–	–
Polyethylene glycol loxenatide	C210H325N55O69S(C2H4O)2n	38	0.1 mg/week	–	–
Benarutide	C149H225N39O46	29	0.3 mg/day	–	–

Table 6 Types of Sodium–glucose cotransporter 2 inhibitors and their recommended clinical dosage

Name	Molecular formula	Recommended initial dosage	In China, Listed or not	Recommended dosage for prediabetes	Ref.
Canagliflozin	C24H25FO5S	100 mg/day	No	–	–
Dapagliflozin	C21H25CIO6•C3H8O2	5 mg/day	Listed	10 mg/day	Lundkvist et al[63]
Empagliflozin	C23H27CIO7	10 mg/day	No	10 mg/day	Lee et al[64]
Ipragliflozin	C21H21FO5S	50 mg/day	No	–	–
Luseogliflozin	C23H30O6S	2.5 mg/day	No	–	–
Tofogliflozin	C22H26O6	5 mg/day	No	40 mg/day	Pafili et al[65]

Table 7 Types of Sodium–glucose cotransporter 2 inhibitors and clinical research results

Name	Ref.	Participants	Grouping and dosage	Result	Conclusion
Metformin	O’Brien et al[32]	92	Metformin group (850 mg/daily), standard diet group	Compared with the standard diet group, the metformin group lost an average of 1.1% body weight, and a normal blood glucose ratio of 28.7% was restored	Reduces weight and restores normal blood glucose levels in prediabetics
Metformin	Tavlo et al[51]	183	1500-2000 mg/d over 12 wk	The impaired glucose tolerance remission rate was 32%	Improves postprandial insulin secretion
Metformin + exenatide	Tavlo et al[51]	183	Metformin: 1500-2000 mg/d; exenatide: 10-20 μg/d over 12 wk	The impaired glucose tolerance remission rate was 64%	Combined administration of drugs is more effective in alleviating glucose tolerance compared with monotherapy
Exenatide	Tavlo et al[51]	183	10-20 μg/d over 12 wk	Impaired glucose tolerance remission rate of 56%	Improves postprandial insulin secretion
Liraglutide	le Roux et al[34]	749	Placebo group (n = 749), liraglutide group (n = 1505, 3 mg/d) over 160 wk	4.2% weight loss and 2.7 times longer onset of diabetes in the liraglutide group than the placebo group	3 mg liraglutide reduces weight gain and diabetes risk
Liraglutide	Pi-Sunyer et al[141]	3731	Placebo (n = 1244), liraglutide (n = 2487, 3 mg/d) over 56 wk	Body weight in the liraglutide group decreased by 36.1%; glycated hemoglobin, fasting blood glucose, and fasting insulin were reduced; and the prevalence of diabetes was reduced, compared with the placebo group	3 mg liraglutide may reduce the incidence of urine disease
Dapagliflozin	Veelen et al[142]	30	Dapagliflozin (2 mg/d) vs placebo, over 10 wk	The plasma glucose level was reduced in the dapagliflozin group compared with the placebo group, and no extensive changes were observed in the glycogen and lipid content of the liver	Dapagliflozin improves fat oxidation and exhibits a marked hypoglycemic effect

Table 8 Selected vitamin D-rich foods and their vitamin D content

Food	Vitamin D content
Fresh shiitake mushrooms (0.0992 kg)	600-1000 IU D2
Sun-dried shiitake mushrooms (0.0992 kg)	600-1000 IU D2
Egg yolk	20 IU D3, 0.2-0.8 μg 25-(OH)D
Cod liver oil (0.006 kg)	400-1000 IU D3
Beef liver (0.4536 kg)	0-2500 IU D3, 0.3-3.5 μg 25-(OH)D
Beef muscle (0.4536 kg)	0-180 IU D3, 0.1-2.6 μg 25-(OH)D
Pork muscle (0.4536 kg)	10-250 IU D3, 0-31.4 μg 25-(OH)D

IU: International Unit; D2: vitamin D2; D3: vitamin D3.