Genetics of diabetes

Table 1 List of various circulating microRNAs reported in diabetes mellitus individuals

Mechanism/pathway (diabetes type)	Expression of miRNAs	Ref.
Endothelial dysfunction (T2DM)	↑miR-28-3p	[87]
	↓miR-24
	↓miR-21
	↓miR-20b
	↓miR-15a
	↓miR-126
	↓miR-191
	↓miR-197
	↓miR-223
	↓miR-320
	↓miR-486
	↓miR-150
	↓miR-29b
	↓miR-107
	↓miR-132
	↓miR-144
Glucose metabolism (T2DM)	↑miR-9	[88]
	↑miR-29a
	↑miR-30d
	↑miR-34a
	↑miR-124a
	↑miR-146a
	↑miR-375
Inflammation (T2DM)	↓miR-146a	[89]
Glucose metabolism (T2DM)	↑miR-27a	[90]
	↑miR-320a
Glucose metabolism (T2DM)	↓miR-126	[91-93]
Inflammation (T2DM)	↓miR-103b	[94]
Inflammation (T2DM)	↓miR-126-3p	[95]
	↓miR-21-5p
Inflammation (T2DM)	↓miR-126	[96]
Endothelial dysfunction (T2DM)	↓miR-126	[97]
	↓miR-26a
Glucose metabolism (T2DM)	↓miR-21	[98]
Inflammation (T2DM)	↓miR-126-3p	[99]
Endothelial dysfunction (T2DM)	↓miR-24	[100]
Platelet reactivity (T2DM)	↓miR-223	[101]
	↓miR-26b
	↓miR-126
	↓miR-140
Glucose metabolism (T2DM)	↑miR-375	[102]
	↑miR-9
Glucose metabolism (T2DM)	↑miR-30a-5p	[103]
	↑miR-150
	↓miR-103
	↓miR-28-3p
	↓miR-29a
	↓miR-9
	↓miR-15a
	↓miR-126
	↓miR-145
	↓miR-375
	↓miR-223
	↓miR-133
	↓miR-107
Endothelial dysfunction (miR-126); hypoxia (miR-210) (T2DM)	↓miR-126	[104]
	↑miR-210
Angiogenesis (T2DM)	↑miR-193b-3p	[105]
	↑let-7i-5p
	↑miR-199a-3-5p
	↑miR-26b-5p
	↑miR-30b-5p
	↑miR-374a-5p
	↑miR-20a-3p
	↑miR-26a-5p
	↑miR-30c-5p
	↓miR-409-3p
	↓miR-95-3p
Apoptosis (T1DM)	↑miR-21	[106,107]
	↓miR-23a-3p	[108]
	↓miR-23b-3p
	↓miR-149-5p
Inflammation (T1DM)	↑miR-101a	[109]
	↑miR-30b
-cell dysfunction (T1DM)	↑miR-106b-5p	[110,111]
	↑miR-222-3p
	↑miR-181a
T-cell dysfunction (T1DM)	↑miR-26a	[112]
	↑miR-98	[113]
	↑miR-23b
	↑miR-590-5p
-cell lymphopoiesis (T1DM)	↑miR-34a	[114]
DNA damage checkpoint (T1DM)	↑miR-200	[115]
Apoptosis (T1DM)	↓miR-144	[116]
Autoimmune imbalance (T1DM)	↓miR-146a	[117]
MODY	↑miR-103	[118]
MODY	↑miR-224
Glucose metabolism (GDM)	↑miR-222	[119]
	↑miR-98	[120]
	↑miR-518d	[121]
	↑miR-340	[122]
	↑miR-130b, miR148a	[123]
-cell dysfunction (GDM)	↑miR-33a-5p	[124]
	↑miR-330-3p	[125]
	↓miR-494	[126]
	↓miR-96	[127]
	↓miR-221	[128]

miRNAs: MicroRNAs; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus; MODY: Maturity-onset diabetes of young.

Table 2 Studies on polygenic risk score for type 1 diabetes mellitus and type 2 diabetes mellitus

Diabetes type	SNPs	AUC for PRS	Ethnicity	Ref.
T1DM	41	0.87	Caucasian	[140]
T1DM	30	0.88	Caucasian	[141]
T1DM + T2DM	99	0.89	Caucasian
T1DM	32	0.86	Caucasian	[142]
T1DM	32	0.90	Caucasian Hispanic
T1DM	32	0.75	African-American
T1DM	32	0.92	Asian-American
T1DM	67	0.93	Caucasian	[143]
T2DM	3	0.58	Caucasian	[144]
T2DM	18	0.80	Caucasian	[136]
T2DM	16	0.75	Caucasian	[134]
T2DM	18	0.91	Caucasian	[135]
T2DM	22	0.74	Caucasian	[145]
T2DM	62	0.91	Caucasian United States population	[146]
T2DM	1000	0.79	Caucasian	[147]
T2DM	4	0.67	African	[148]
T2DM	7 million	0.73	Caucasian	[149]

SNP: Single nucleotide polymorphisms; AUC: Area under the curve; PRS: Polygenic risk score; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus.

Table 3 Polygenic risk scores studies for gestational diabetes mellitus

Diabetes type	SNPs	OR 95%CI	Ref.
GDM	34 SNPs previously associated with T2DM	1.11 (1.08-1.14)	[150]
GDM	11 SNPs previously associated with T2DM	1.18 (1.10-1.27)	[151]
GDM	150 previously associated with T2DM	1.06 (1.01-1.10)	[152]
GDM	84 SNPs	6.15 (5.03-7.51) top 5%	[153]

SNP: Single nucleotide polymorphisms; OR: Odds ratio; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus.

Table 4 List of phytochemicals used in the prevention and treatment of diabetes and its complications

Phytochemical	Source	Outcomes	Ref.
Curcumin	Curcuma longa	↑Insulin sensitivity, ↓blood glucose levels, and hypoglycemia	[180]
Rutin	Buckwheat (Fagopyrum esculentum)	↓Hepatic glucose production, ↑glucose tolerance	[181]
Resveratrol	Grapes, plums, peanuts, nuts, red wine	Improved insulin signaling, ↑glucose-mediated insulin secretion	[182]
Quercetin	Apples, black tea, berries, capers, red wine, onions	↑Glucose uptake, ↓hepatic glucose production	[182,183]
Genistein	Legumes	Improved lipid glucose metabolism and ↓fasting glucose	[184]
Hesperidin	Orange, lemon	↑Glucose uptake, ↓HbA1c, ↓oxidative stress	[185]
Naringin	Skin of grapefruit and orange	↓Hepatic glucose production, ↓oxidative stress, ↑glucose uptake	[185]
Naringenin	Citrus fruits, tomatoes, cherries, grapefruit, cocoa	↑Glucose uptake, ↓glucose intolerance and reduced blood glucose levels	[186]
Vitamin A, D, and E	Eggs, yellow, red, and green (leafy) vegetables, such as spinach, carrots, sweet potatoes and red peppers. yellow fruit, such as mango, papaya and apricots	↓Glucose intolerance, ↓hyperglycemia	[182]
Fisetin	Strawberry, apple, persimmon, grape, onion, and cucumber	↓Hepatic glucose and ↑glucose metabolism	[187]
Flavonoids	Coffee, guava tea, whortleberry, olive oil, propolis, chocolate, and cocoa	↓Glucose absorption, inhibition of advanced glycation end products	[188]
Isoflavones	Soybean	Improves glucose metabolism	[189]
Catechins	Tea leaves and red wine	Promote insulin sensitivity	[190]
Hydroxycinnamic acids	Fruits and vegetables, especially the outer part of ripe fruits	Promote glucokinase activity	[191]
Caffeoylquinic	Potatoes, eggplants, peaches, prunes, and coffee beans	Promote insulin response	[192]
Anthocyanins and anthocyanidins	Berries, eggplants, avocado, oranges, olives, red onion, fig, sweet potato, mango, and purple corn	Promote blood glucose regulation	[193]
Stillbenoids	Grapevine, berries, and peanuts	Promote pancreatic -cell and hepatoprotective activity	[194]

HbA1c: Glycated hemoglobin.