Table 1.

Description of the articles, 2019.

Source	Study site	Sample characteristics	Study design	Results
Gulcan et al. [30]	Kutahya/Peru	91 participants (51 asthma patients and 40 nonasthmatic controls). Participants with asthma: $\stackrel{⌣}{\mathbf{x}}$  = 40.3 ± 7.8; nonasthmatic controls: $\stackrel{⌣}{\mathbf{x}}$  = 39.5 ± 6.7.	Cross-sectional design	Changes in fasting blood glucose levels and 2 hours after coffee, plasma insulin, HOMA-IR and LDL-C levels were greater in patients with asthma than in nonasthma controls (p < 0.005).
Hashemzadeh and Movahed, [29]	Arizona/USA	845,748 participants (293,124 with diabetes and without hypertension and 552,625 with hypertension and without diabetes as controls); asthma and diabetes: 13,243; asthma and hypertension: 16,036. Patients with T2DM $\stackrel{⌣}{\mathbf{x}}$ = 65.8 ± 11.3 and the control group NON-T2DM $\stackrel{⌣}{\mathbf{x}}$ = 64.8 ± 12.6; men: 97.8% in the T2DM group and 97.4% in the control group.	Cross-sectional design	Asthma was present in 4.5% of patients with T2DM and 2.9% in the control group. After adjusting for covariables such as hyperlipidemia and smoking, T2DM remained independently associated with asthma (OR = 2.99; 95% CI: (2.92–3.06); p < 0.001).
Faul et al. [34]	California/USA	10 male adults with DMT2 and asthma or COPD (05 with asthma and 05 with COPD). All participants: $\stackrel{⌣}{\mathbf{x}}$ = 64 ± 52–76. All male.	Prospective, randomized, double-blind, double-placebo, placebo-controlled study	The mean of HbA1c after 06 weeks of treatment with fluticasone vs. treatment with oral montelukast was significantly higher than the mean of the baseline but was not considered clinically relevant (mean differences = 0.11 and −0.14, respectively, p=0.025).
Song et al. [15]	Boston/USA	38,570 women (3,368 asthma only; 1,808 COPD only; 32,248 controls-no). Mean age of asthma only: 53.8.	Prospective cohort	Women who have ever reported asthma were associated with an increased risk of diabetes: RR = 1.37 (95% CI: [1.20–1.57]). This association was not significantly modified by confounders such as age, smoking, or BMI.
Suissa et al. [33]	Quebec/Canada	358,417 participants treated for respiratory disease (30,167 had diabetes-incidence rate: 14.2/100/year) and 2,099 progressed from oral hypoglycemic to insulin-incidence rate: 19.8/1000/year). Participants diagnosed with diabetes: $\stackrel{⌣}{\mathbf{x}}$ = 66.3 ± 15 (cases and control); participants with progression to diabetes: $\stackrel{⌣}{\mathbf{x}}$ = 65.5 ± 16.0 (cases) and $\stackrel{⌣}{\mathbf{x}}$ = 65.4 ± 15.6 (controls); male with diabetes: 41.4% (cases) and 38.7 (controls); progressed to insulin = 37.6% (cases) and 37.5% (controls).	Prospective cohort	The use of CIS was associated with a 34% increase in the incidence of diabetes (RR = 1.34; 95% CI: 1.29–1.39) and a 34% progression rate of the oral hypoglycemic to insulin (RR = 1.34; 95% CI: [1.17–1.53]); the risks were higher with the higher doses of CIS, equivalent to fluticasone 1000 µg/day or more (RR = 1.64; 95% CI: (1.52–1.76) and RR = 1.54; 95% CI: (1.18–2.02), respectively)
Thomsen et al. [28]	Copenhagen/Denmark	34,782 Danish twins (3,004 with asthma and 31,778 nonasthma controls). Average age: 20–71 years, being 54% women and 46% men.	Cross-sectional design	The risk of asthma was increased in individuals with T2DM compared to nondiabetic individuals, both in men (13.5% vs. 7.5%; p=0.001) and in women (16.6% vs. 9.6%; p=0.001).
Yun et al. [19]	Rochester, Minnesota/USA	7,176 participants (asthma = 2,392 and nonasthma controls = 4,784). Age at onset of asthma: $\stackrel{⌣}{\mathbf{x}}$ = 15.1 ± 20.5; adults ≥18 years: 1,310 (55%) asthma group; 2,690 (56%) control group; male = 1,356 (57%) asthma group; 2,712 (57%) controls.	Retrospective cohort	Asthma is associated with an increased risk of diabetes (OR = 2.11; 95% CI: (1.43–3.13); p < 0.001).
Rodbard et al. [27]	Maryland/USA	8,582 baseline participants: 7,970 non-DM2 and 622 transitioned to T2DM. Non-T2DM participants: $\stackrel{⌣}{\mathbf{x}}$ = 53.7 ± 16.5; made the transition to T2DM: $\stackrel{⌣}{\mathbf{x}}$ = 58.3 ± 12.5; non-T2DM women = 61.5% and women transitioning to T2DM = 61.3%.	Prospective cohort	Self-reported asthma was associated with an increased risk of transition to T2DM (OR = 1.33; 95% CI: [1.04–1.70]; p=0.020).
Koskela et al. [32]	Kuopio/Finland	153 patients (109 with asthma and 44 with COPD); 23 with previous diabetes diagnosis and 103 without diabetes diagnosis; without diabetes: 103 with hyperglycemia and 27 with euglycemia. Participants with diabetes: 56% male and $\stackrel{⌣}{\mathbf{x}}$ = 65.0 ± 12.9; participants without diabetes with hyperglycemia: 55% male and $\stackrel{⌣}{\mathbf{x}}$  = 65.9 ± 15.0.	Cross-sectional design	Of the entire study population, 125 (82%) demonstrated hyperglycemia: 103 (79%) among patients without diabetes and 22 (96%) among patients previously diagnosed with diabetes. The prevalence of hyperglycemia did not differ among patients with asthma and COPD.
Mueller et al. [14]	Republic of Singapore/Southwest Asia	42,842 men and women (873 with asthma and 41,969 nonasthma controls). Men and women: nonasthma $\stackrel{⌣}{\mathbf{x}}$ = 55.2 ± 7.6; asthma >18 years: $\stackrel{⌣}{\mathbf{x}}$ = 56.7 ± 8.1; asthma <18 years: $\stackrel{⌣}{\mathbf{x}}$ = 52.5 ± 6.5.	Prospective cohort	Asthma was associated with a 31% increased risk of diabetes incidence (OR = 1.31; 95% CI: [1.00–1.72]). The association was attenuated after adjusting for BMI (OR = 1.25; 95% CI: [0.95–1.64]).
Koskela et al. [39]	Kuopio/Finland	153 participants: 110 (72%) with asthma and 43 (28%) with COPD; 23 with a medical diagnosis of diabetes; 20 diagnosed during screening; 110 without diabetes. Diabetes diagnosis: $\stackrel{⌣}{\mathbf{x}}$ = 64.4 (59.1–69.9), 52% male; diabetes screening: $\stackrel{⌣}{\mathbf{x}}$ = 68.8 (64.8–72.8), 70% male; nondiabetes: $\stackrel{⌣}{\mathbf{x}}$ = 64.3 (61.3–67.2), 51% male.	Prospective cohort	Fasting hyperglycemia was detected in 91% of patients diagnosed with diabetes, 90% of patients screened for diabetes, and 63% of nondiabetes (p = 0.003). Previously diagnosed diabetes was associated with high mortality (aOR = 1.04; 95% CI: (0.50-A 2.12).
Wytrychowsky et al. [20]	Wroclaw/Poland	88 patients hospitalized for acute asthma exacerbation (24 with glucose disorders and 64 controls without hyperglycemia). Group A = 11 patients/intravenous insulin: $\stackrel{⌣}{\mathbf{x}}$ = 61.4 ± 11.0; group B = 13 patients/ subcutaneous insulin; $\stackrel{⌣}{\mathbf{x}}$ = 53.7 ± 12.5; group C = 64 patients without hyperglycemia/control group: $\stackrel{⌣}{\mathbf{x}}$ = 48.3 ± 14.4.	Prospective, randomized study	Newly diagnosed hyperglycemia and/or diabetes hinders recovering from acute asthma exacerbation requiring hospitalization, prolonging hospital stay compared to patients who do not have glucose metabolism disorders.
Sweeney et al. [23]	Belfast/United Kingdom	7,195 participants (severe asthma: 808; mild/moderate asthma: 3,975; nonasthma control: 2,412). All participants: $\stackrel{⌣}{\mathbf{x}}$ = 58 ± 17; severe asthma: $\stackrel{⌣}{\mathbf{x}}$ = 58 ± 18; mild/moderate asthma: $\stackrel{⌣}{\mathbf{x}}$ = 58 ± 16; nonasthma control: $\stackrel{⌣}{\mathbf{x}}$ = 58 ± 17.	Cross-sectional design	In comparison with mild/moderate asthma, patients with severe asthma had higher morbidity rates when exposed to systemic corticosteroids (T2DM: 10% vs. 7%, OR = 1.46; 95% CI [1.39–2.56; p < 0.001]).
Verbovoy et al. [31]	Samara/Russia	53 women (27 with a diagnosis of DM2; 26 with a combination of T2DM and asthma; 23 from the control group). Women diagnosed with T2DM ($\stackrel{⌣}{\mathbf{x}}$ = 60.15 ± 0.92 years); combination of T2DM and asthma ($\stackrel{⌣}{\mathbf{x}}$ = 61.23 ± 0.95 years); control group (x = 51.26 ± 1.73).	Cross-sectional design	Hyperleptinemia, hyperresistinemia, lower adiponectin concentrations, higher levels of proinflammatory IL-6 and anti-inflammatory IL-10, and significantly elevated blood glucose levels were found in patients with T2DM and asthma than in the control group. These changes occurred in the presence of subclinical inflammation.
Klein et al. [21]	California/USA	2,645 men and women (659 with lung disease (asthma, bronchitis, and COPD) and T2DM; 1,986 with lung disease and non-T2DM). Participants with pulmonary disease and T2DM: $\stackrel{⌣}{\mathbf{x}}$ = 53.8 (52.3–55.2) and with lung and non-T2DM disease: $\stackrel{⌣}{\mathbf{x}}$ = 39.3 (38.4–40.2; women with lung disease and T2DM: $\stackrel{⌣}{\mathbf{x}}$ = 63.4 (61.9–64.8) and with lung disease and non-T2DM: $\stackrel{⌣}{\mathbf{x}}$ = 58.2 (55.8–60.6).	Multicenter and observational study with cross-sectional analyses	Among Hispanics/Latinos with lung disease, those with T2DM have lower mean FEV1 and FVC values than those without T2DM (VEF1 3,00; IC: [2,96–3,04] vs. 3,10; IC95%: [3,09–3,11], p < 0.01) e CVF (3,62; 95% IC: [3,59–3,66] vs. 3,81; 95% IC: [3,79–3,83], p < 0.001).
Li et al. [38]	Taipei/Taiwan	1,332 patients with asthma and diabetes (444/33.3% using metformin and 888/66.6% non-metformin). Participants using metformin: 64 (10.4%); female: 268 (60.4%); male: 176 (39.6%); non-metformin: 64 (10.4%); female: 536 (60.4%); male: 352 (39.6%).	Retrospective cohort	In comparison with nonusers, metformin users had a lower risk of hospitalization related to asthma (OR = 0.21, 95% CI: [0.07–0.63]) and exacerbation of asthma (OR = 0.39, 95% CI: [0.19–0.79]).
Veryomenko and Bezditko [37]	Karkov/Ukraine	47 patients with asthma and T2DM before and after treatment. Treatment (group 1, n = 28) and comparison (group 2, n = 19). Data not shown.	Intervention study	The use of the L-arginine complex and TB preparations against the use of basic therapy in patients with asthma and T2DM produced better control over the disease, faster elimination of manifestations of obstruction, clinical spirographic remission, improved quality of life, correction of disorders in hemocoagulation, fibrinolysis, and functional status of the endothelium.
Baek et al. [16]	Korea	13,154,348 (2,335,303 with asthma and 10,819,045 controls without asthma). Nonasthma: $\stackrel{⌣}{\mathbf{x}}$ = 48 ± 12.3; asthma: $\stackrel{⌣}{\mathbf{x}}$ = 52 ± 13.1.	Cross-sectional design	Diabetic patients with retinopathy had an increased risk of developing asthma (OR: 1.067; 95% CI: [1.053–1.081]). Diabetic patients without retinopathy had a lower risk of developing asthma compared to nondiabetics (OR: 0.943; 95% CI: [0.939–0.948]).

$\stackrel{⌣}{\mathbf{x}}$: mean; ±: standard deviation; HOMA IR: homeostasis model assessment-insulin resistance; LDL-C: low density lipoprotein cholesterol; OR: odds ratio; aOR: odds ratio adjusted; CI: confidence interval; HbA1c: glycated hemoglobin; RR: relative risk; BMI: body mass index; T2DM: diabetes mellitus type 2; CIS: inhaled corticosteroid; COPD: chronic obstructive pulmonary disease; IL: interleukin; FEV1: forced expiratory volume in the first minute; FVC: forced vital capacity; TB: tiotropium bromide.