Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

Table 1 Short summary of different definitions of the term: Insulin resistance

	Ref.
Insulin resistance is the impaired sensitivity of tissue to the action of insulin	[5]
Insulin resistance signifies the inability of insulin at physiological concentrations to exert its normal metabolic actions.	[6]
Insulin resistance is a diminished ability to keep the serum glucose low with insulin levels in the normal range.	[7]
Insulin resistance is an integral concept characterizing all cases of a reduced biological effect of insulin with its normal concentration and activity.	[8]
Insulin resistance is defined as a state of reduced responsiveness to normal circulating concentrations of insulin.	[9]
Insulin resistance refers to state in which physiological concentrations of insulin are poorly effective.	[10]
Insulin resistance is characterized by a reduced sensitivity of body cells to the actions of insulin.	[11]
Insulin resistance is defined as the inability of cells to efficiently respond to stimulation by insulin.	[12]

Table 2 Values of glucose effectiveness and insulin sensitivity¹ for minimal models

Units	Control subjects	Type 2 diabetes	P value	Δ (%)	Compartment	Tracer	Ref.
SG
min-1	0.016 ± 0.001	0.010 ± 0.001	< 0.01	37.5	One	No	[13]
	0.020 ± 0.002	0.013 ± 0.001	< 0.05	35.0	One	No	[14]
	0.023 ± 0.012	0.016 ± 0.009	< 0.001	30.4	One	No	[15]2
h-1	1.20 ± 0.16	0.81 ± 0.11	< 0.001	32.5	One	No	[16]
	0.41 ± 0.04	0.33 ± 0.02	< 0.001	19.5	Two	13C	[16]
	0.52 ± 0.05	0.37 ± 0.02	< 0.001	28.8	Two	2H	[16]
SI
10-4·min-1· (mU/L)-1	11.8 ± 2.6	6.7 ± 0.8	< 0.01	43.2	One	No	[14]
	13.45 ± 11.12	5.31 ± 3.98	< 0.01	60.5	One	No	[15]2
pmol·L-1·(h-1)	0.0062 ± 0.0006	0.0019 ± 0.0006	< 0.01	69.4	One	No	[16]
	0.0082 ± 0.0012	0.0036 ± 0.0006	< 0.001	56.1	two	13C	[16]
	0.0098 ± 0.0013	0.0042 ± 0.0008	< 0.001	57.1	Two	2H	[16]

¹We used the conversion factor: 1 mU/L = 6.00 pmol/L;

²More than 10 years before the development of type 2 diabetes. S_G: Glucose effectiveness; S_I: Insulin sensitivity.

Table 3 Two-compartment minimal model analysis of the relative contribution of glucose effectiveness to the glucose restoration rate of type 2 diabetes during basal state

	Units	13C	2H
SG	h-1	0.33 ± 0.02	0.37 ± 0.02
SI	h-1·(pmol/L)-1	0.0036 ± 0.0006	0.0042 ± 0.0008
SI × 1.8 × 6	h-1	0.0389 ± 0.0056	0.0454 ± 0.0086
SG/(SG + SI × 10.8)	%	89.4	89.1

S_G: Glucose effectiveness; S_I: Insulin sensitivity.

Table 4 Experimental data of fully hydrated fluid phase phosphatidylcholine lipid bilayers

	DLPC	DMPC	DPPC	DOPC	PDPC
Reference	25	25	26,27	26	28
Fatty acid structure	[C12:0]2	[C14:0]2	[C16:0]2	[C18:1]2	C16:0;C22:6
Temperature (˚C)	30	30	50	30	30
Area A per lipid molecule (Å)2	63.2	60.6	64.0	72.5	74.8
Carbon interchain distance (Å)	4.49	4.39	4.51	4.80	4.88
Interaction energy U (kJ/mol)		-0.607			-0.379
UI	0	0	0	100	300

DLPC: Dilauroylphosphatidylcholine; DMPC: Dimyristoylphosphatidylcholine; DPPC: Dipalmitoyl-phosphatidylcholine; DOPC: Dioleoylphosphatidylcholine; PDPC: Palmitoyl-docosahexaenoic-phosphatidylcholine; UI: Unsaturation index.

Table 5 Erythrocyte acyl composition of phospholipids and unsaturation index of control individuals, individuals with impaired glucose tolerance, and individuals with gestational diabetes mellitus¹

Biochemical characteristics	IGT			GDM
	Control persons(n = 42)	Persons with IGT (n = 28)	Δ (%)	Control persons(n = 61)	Persons with GDM(n = 53)	Δ (%)
PC
Total SFAs (%)	46.4	49.2	+ 6.0	42.5	48.3	+24.6
Total MUFAs (%)	17.8	19.1	+7.3	13.1	15.8	+20.6
Total PUFAs (%)	26.8	22.3	-12.5	37.2	31.1	-16.4
UI	92	79.5	-13.6	148.1	114.8	-22.5
PE
Total SFAs (%)	38.4	40.5	+5.5	24.6	27.2	+10.6
Total MUFAs (%)	27.5	30.1	+9.5	18.6	20.1	+8.1
Total PUFAs (%)	34.6	29.4	-15.0	37.8	33.7	-10.8
UI	167.4	147.1	-12.1	177.6	159.4	-10.2

¹Ex-post calculations performed by the author are based on the original data listed by Min et al[32,33]. The calculations of the biochemical characteristics are shown in Supplementary Tables 1 and 2. UI: Unsaturation index; IGT: Impaired glucose tolerance; GDM: Gestational diabetes mellitus; PC: Phosphatidylcholine; PE: Phosphatidylethanolamine; SFA: Saturated fatty acid; MUFA: Mono-unsaturated fatty acid; PUFA: Poly-unsaturated fatty acid.

Table 6 Acyl composition (% of total acyl chains) of membrane phospholipids and unsaturation index in fathead minnow (Pimephales promelas) muscle¹

Biochemical characteristics	15 ˚C	25 ˚C	30 ˚C
Total SFAs (%)	17.8	19.9	38.4
Total MUFAs (%)	16.1	16.1	26.6
Total PUFAs (%)	65.7	61.5	34.9
UI	349.9	325.9	189.9

¹Ex-post calculations of the biochemical characteristics are performed by the author and based on the original data listed by Fadhlaoui et al[60]. The calculations of the biochemical characteristics are shown in Supplementary Table 3. UI: Unsaturation index; SFA: Saturated fatty acid; MUFA: Mono-unsaturated fatty acid; PUFA: Poly-cis-unsaturated fatty acid.

Table 7 Thought experiment of multi-celled development of a single-celled, cube-shaped eukaryotic cell, which grows through cell division in a Cartesian coordinate system with the same speed in all three directions, and exchanges with its environment per unit-cell one heat unit per time unit[63]

Growth of cubic species	Number of unit cubes	Total cube
		Required number of heat units to exchange	Number of unit-cube surface planes
Original cube	1	1	6
First generation	8 (23)	8 (23)	24 (6 × 22)
Second generation	27 (33)	27 (33)	54 (6 × 32)
Third generation	64 (43)	64 (43)	96 (6 × 42)
Fourth generation	125 (53)	125 (53)	150 (6 × 52)

Table 8 Erythrocyte acyl chain composition in phospholipids and unsaturation index of control individuals, people with type 2 diabetes without retinopathy, and people with type 2 diabetes with retinopathy¹

Biochemical characteristics	Control individuals (n = 18)	Individuals with type 2 diabetes without retinopathy (n = 14)	Individuals with type 2 diabetes with retinopathy(n = 46)
Total SFAs (%)	42.0	44.2	46.9
Total MUFAs (%)	18.8	21.7	21.3
Total PUFAs (%)	38.0	31.9	29.5
UI	155.4	134.3	123.3

¹Ex-post calculations performed by the author (see appendix) are based on the original data listed by Koehrer et al[83]. The calculations of the biochemical characteristics are shown in Supplementary Tables 5 and 6. SFA: Saturated fatty acid; MUFA: Mono-unsaturated fatty acid; PUFA: Poly-unsaturated fatty acid; UI: Unsaturation index.