Type 2 diabetes mellitus is more commonly well controlled in younger men compared to older men

Abstract

Aims: Type 2 Diabetes Mellitus (T2DM) is nearly epidemic worldwide. Greater skeletal muscle mass in men is protective against the development of T2DM compared to women, however, nutritional diversity, stress levels and other factors also affects this situation. In present retrospective study, we aimed to observe diabetic control level, metabolic parameters and general characteristics of type 2 diabetic men and to compare these values in middle aged and elderly diabetic population.

Methods

The male patients with T2DM that admitted to the outpatient internal medicine clinics of our institution between November 2018 and April 2019 were included to the study. According to the age, study population divided into two groups; either younger than 60 years (group I) and 60 years or older (group II). Study parameters were compared between study groups.

Results

Fasting plasma glucose (FPG) and glycated Hb level (HbA1c) of group I were lower than those of the group II (p = 0.004 for FPG and p = 0.048 for HbA1c). Control level of T2DM was defined as well controlled in 20 (29%) patients in group I and 5 (10.9%) patients in group II (p = 0.02).

Conclusion

Physicians should aware that well controlled T2DM is more common among younger diabetic men compared to older men and try to enhance diabetic regulation level in elderly men by interventions that aimed to improve skeletal muscle or by pharmacologic agents.

Keywords:

• Type 2 diabetes mellitus
• elderly men
• HbA1c
• fasting glucose

Introduction

Type 2 diabetes mellitus (T2DM) has important amount of burden in health and is about to reach a worldwide epidemic in near future [1]. Novel studies about T2DM aimed to discover alternative and better therapeutic options [2]. Although a number of medications installed and still being developed in the management of the disease, diet and exercise have utmost importance in anti-diabetic treatment.

Since women and men have different kind of alimentation, work in diverse conditions, have distinct habits and stress level, development of T2DM, awareness of the disease, time of diagnosis, efficacy of the treatment are affected by the gender [3]. Body mass composition and energy metabolism are regulated by involving of sex hormones as well as other factors. Because traditional measure of body mass index underestimates the muscle amount in men, men with greater muscle mass could be classified as obese and subjects with less muscle but more fat could be defined as normal [4]. Men tend to have greater muscle mass compared to women, which is protective against development of T2DM. Erectile dysfunction is a major concern in type 2 diabetic men [5,6].

Advancing age induces visceral fat accumulation and leads to deterioration in lipid metabolism by increasing the production of free fatty acids that plays pivotal role in decreased insulin sensitivity [7]. Physical inactivity, which is common in older diabetic subjects, causes decline in skeletal muscle mass of the body, and since skeletal muscles are responsible of great amount glucose utilization, insulin resistance develops following the loss in skeletal muscle mass [8]. On the other hand, advanced age has negative effects in insulin production because pancreatic insulin secretion decreases by aging in subjects with T2DM [9].

In present retrospective study, we aimed to observe general characteristics, anthropometric measures, regulation level of the disease and laboratory metabolic parameters of elderly men with T2DM and compare those values to the younger type 2 diabetic men.

Methods

The male patients with T2DM that admitted to the outpatient internal medicine clinics of our institution between November 2018 and April 2019 were included to the study. Local ethics committee has been approved the study (id no: 2019–215).

Subjects with other types of diabetes mellitus, active infection, inflammatory disorders, and cancer are excluded.

According to the age, study population divided into two groups; either younger than 60 years (group I) and 60 years or older (group II).

Age, gender, blood pressure, height, weight, waist circumference, anti-diabetic treatment, presence of comorbidities (hypertension, coronary heart disease, congestive heart failure, cerebrovascular disease, chronic obstructive pulmonary disease), duration of diabetes was recorded from the patient files. Body mass index (BMI) is calculated with simply division of weight in kg by the square of height in meters.

Serum creatinine, uric acid, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), albumin, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride levels were obtained from the database of the institution. All of these values were recorded for comparison.

Data was analyzed with SPSS software (SPSS 15.0 for Windows, IBM Co, Chicago, IL, USA). Categorical variables were conducted with chi-square test and expressed as percentage. Pearson correlation analyze test was used to observe correlation among study parameters. Distribution of variables in study groups were conducted with Kolmogorov–Smirnov test. Variables with normal distribution were compared with independent samples t test and expressed as mean ± standard deviation. Variables without normal distribution were compared with Mann–Whitney U test and expressed as median (minimum-maximum). A p values lower than 0.05 was considered as statistically significant.

Results

One hundred and fifteen diabetic men enrolled to the study; 69 were younger than 60 years of age and 46 were 60 years or older. Mean age of the groups I and II were 52 ± 6 and 68 ± 6 years, respectively (p < 0.001).

While 21 0f 69 (30%) patients in group I had comorbid conditions, there were 16 (35%) subjects with comorbidities in group II (p = 0.63). Five (7.2%) subjects in group I and 7 (15.2%) subjects in group II had diabetic retinopathy (p = 0.17). Twenty (29%) subjects in group I and 17 (37%) subjects in group II had diabetic neuropathy (p = 0.37). Nineteen (27.5%) subjects in group I and 17 (37%) subjects in group II had diabetic nephropathy (p = 0.29). There was no significant difference between group I and II in terms of diabetic microvascular complications.

Height (p = 0.95), weight (p = 0.41), waist circumference (p = 0.50), BMI (p = 0.91), serum creatinine (p = 0.21), uric acid (p = 0.60), albumin (p = 0.37), total cholesterol (p = 0.17), LDL-cholesterol (p = 0.15), HDL-cholesterol (p = 0.16), and triglyceride (p = 0.65) levels were not significantly different between groups I and II.

Both median systolic (110 (90–170) mmHg in group I versus 130 (110–180) mmHg in group II) and diastolic (80 (50–100) mmHg in group I versus 80 (60–100) mmHg in group II) blood pressures were significantly higher in group II compared to those in group I (p < 0.001 for systolic and p = 0.002 for diastolic blood pressure).

Fasting plasma glucose of group I (137 (80–320) mg/dL) was lower than that of the group II (159 (98–459) mg/dL). The FPG difference between groups I and II was statistically significant (p = 0.004).

Median HbA1c of group I (8.2 (6.4–13)%) was lower than that of the group II (8.3 (5.1–11)%). The HbA1c difference between groups I and II was statistically significant (p = 0.048). General characteristics and laboratory data of groups I and II are summarized in Table 1.

Table 1. General characteristics and data of the groups I and II.

	χ^2
	Group I	Group II	p
Comorbidities
Absent (n%)	48 (70)	30 (65)	0.63
Present (n%)	21 (30)	16 (35)
Diabetic retinopathy
Absent (n%)	64 (93)	39 (85)	0.17
Present (n%)	5 (7)	7 (15)
Diabetic neuropathy
Absent (n%)	49 (71)	29 (63)	0.37
Present (n%)	20 (29)	17 (37)
Diabetic nephropathy
Absent (n%)	50 (72.5)	29 (63)	0.29
Present (n%)	19 (27.5)	17 (37)
Well-controlled T2DM
Absent (n%)	49 (71)	41 (89)	0.02
Present (n%)	20 (29)	5 (11)
	Mean ± SD
Age (years)	52 ± 6	68 ± 6	<0.001
	Median (Min.–Max.)
Systolic BP (mmHg)	110 (90–170)	130 (110–180)	<0.001
Diastolic BP (mmHg)	80 (50–100)	80 (60–100)	0.002
Height (m)	1.7 (1.5–1.83)	1.7 (1.54–1.79)	0.95
Weight (kg)	80 (48–117)	83 (56–112)	0.41
Waist circumference (cm)	102 (74–130)	101 (85–141)	0.50
BMI (kg/m^2)	28.1 (16.6–38.4)	28.4 (20.3–40.4)	0.91
Serum creatinine (mg/dL)	0.85 (0.5–1.87)	0.86 (0.6–2.2)	0.21
Uric acid (mg/dL)	5.3 (2.8–8.5)	5.1 (2–8.6)	0.60
Albumin (g/dL)	4.3 (2.7–5.1)	4.3 (3–4.7)	0.37
Total cholesterol (mg/dL)	184 (94–276)	185 (128–280)	0.17
LDL-cholesterol (mg/dL)	113 (42–186)	115 (62–200)	0.15
HDL-cholesterol (mg/dL)	43 (27–87)	40 (29–73)	0.16
Triglyceride (mg/dL)	153 (52–841)	150 (47–850)	0.65
Fasting plasma glucose (mg/dL)	137 (80–320)	159 (98–459)	0.004
HbA1c (%)	8.2 (6.4–13)	8.3 (5.1–11)	0.048

Bold values indicate significantly different p values.

Control level of T2DM was defined as well controlled in 20 (29%) patients in group I and 5 (10.9%) patients in group II. The rate of well controlled T2DM was significantly higher in group I compared to group II (p = 0.02).

Discussion

The primary outcome of present study is younger type 2 diabetic men have greater well controlled disease, compared to older men with type 2 diabetes mellitus. Lower fasting plasma glucose and HbA1c levels in group I compared to group II suggest this result.

The serum triglyceride [10] and LDL cholesterol [11] levels are progressively increase in men by aging while HDL-cholesterol decreases meanwhile before slightly elevates in elderly [12]. Serum triglyceride is the main source of plasma free fatty acid. Plasma free fatty acid levels are increased in conditions that characterized with insulin resistance; such as obesity, metabolic syndrome and type 2 diabetes mellitus and elevation in free fatty acids in serum causes worsening in hyperglycemia and decreasing insulin sensitivity in skeletal muscles [13]. Thus, elevation in blood glucose levels and deterioration in diabetic regulation occur in patients with type 2 diabetes mellitus. However, serum triglyceride levels of study groups in present study were not statistically different.

Skeletal muscle mass make the two of five of whole body mass. It reaches to top by adulthood and thereafter a decline in skeletal muscle mass is observed by aging. Progressive loss of the mass and strength of skeletal muscle mass by advancing age is so called as sarcopenia [14]. Age associated reduction in skeletal muscle mass is a common finding in geriatric age group which is related with adverse events; such as falls, fractures, hospitalization [15]. Another consequence of loss of skeletal muscle is increased insulin resistance. The skeletal muscle release interleukin-6 during contraction which consequently stimulates insulin secretion by increasing the production and secretion of pancreatic glucagon-like peptide-1 [16]. Insulin has beneficial effects in muscle by stimulating the synthesis of protein and by reducing protein degradation [17]. Therefore, resistance to insulin in skeletal muscle in type 2 diabetic subjects may be responsible of the loss of mass and strength of skeletal muscle [18]. Insulin like growth factor, which has important role in protein synthesis is skeletal muscle, is reduced in subjects with type 2 diabetes mellitus [19]. All these mechanisms together contribute to sarcopenia in elderly. Age of group II was significantly advanced compared to group I in present study which could be associated with lower skeletal muscle mass. Although, BMI of the groups I and II were not statistically different, yet, there could be difference in skeletal muscle mass between older and younger subjects in present study. BMI is a widely applied index of obesity based on the weight and height of the person, still, it has some limitations in calculating body mass; such as subjects with greater muscle mass could be defined as obese because of the elevation of body weight and subjects with greater fat tissue but normal weight due to low muscle mass could be defined as to have normal BMI [4]. It is because, by aging, fat tissue increase and skeletal muscle mass reduce even in subjects without significant change in body weight [20].

Another possible mechanism for more common well controlled type 2 diabetes mellitus in younger compared to older men could be the effect of testosterone [21]. Testosterone treatment have beneficial effects on glycaemia [22–24]. Patients with obesity, which is a risk factor for type 2 diabetes mellitus, benefits from testosterone replacement treatment [25]. On contrary, antitestosterone therapy may alter blood glucose control in type 2 diabetes mellitus [26]. Moreover, testosterone have prevented the progression of prediabetic condition to overt diabetes mellitus [27]. Hence, authors found that prediabetes was more common in patients with late onset hypogonadism [28].Type 2 diabetic men have reduced testosterone levels [29]. Moreover, men with raised serum testosterone levels have more than 40% lower risk of developing type 2 diabetes mellitus compared to men without high testosterone levels [30]. Protein synthesis and muscle proliferation are stimulated by testosterone which result in augmentation in skeletal muscle mass [19]. In contrary, pharmacologic interventions in men that reduce circulating testosterone, result in elevated fat mass and reduced basal metabolism rate [31]. Since the testosterone levels of the men reduce by aging [32], this reduction may explain the worse metabolic control in elderly men compared to younger subjects with type 2 diabetes mellitus in present study. Nocturnal hypoglycemia was associated with fasting glucose levels in elderly men [33].

Limitations of present study are relatively small sample size and retrospective design. Lack of serum testosterone and plasma insulin like growth factor levels are also limitations that associated with the retrospective nature of the study. However, better control of type 2 diabetes mellitus in younger compared to older men is an important result of present study.

In conclusion, well controlled type 2 diabetes mellitus is more common among diabetic young men compared to older men. Physicians should aware of this situation and try to enhance diabetic regulation level in elderly men by interventions that aimed to improve skeletal muscle or by pharmacologic agents.

Disclosure statement

No potential conflict of interest was reported by the authors.